Types Of Lymphocytes Research Articles

Pathological images machine learning and prediction of long-term efficacy for immunotherapy in small cell lung cancer.

8578 Background: In development of effective treatment such as immune checkpoint inhibitors (ICIs) among patients with small-cell lung cancer (SCLC), the absence of biomarkers is critical. Tumor-infiltrating lymphocytes are the main activator of antitumor immunity and could be a promising biomarker if TIL can be objectively assessed throughout the whole tumor immune microenvironment (TIME). To evaluate TIME, pathological assessment is one of the easiest ways. Recently, several studies showed that machine learning analysis can assess type of lymphocytes and their localization in pathological images. Here, we aimed to develop a novel biomarker to predict efficacy of ICI in SCLC using machine learning of pathological images. Methods: This study was a biomarker analysis of the APOLLO study which was 32-centered, prospective cohort study of patients with extensive-stage SCLC who received chemo-immunotherapy as the first-line treatment between September 2019 and September 2020. The patient who can provide sufficient tumor tissue sample from the primary tumor were enrolled. We trained a classifier which predicts 365-day progression-free survival (PFS) by all three types of pathological images (hematoxylin and eosin, programmed death-ligand 1, and CD8_FoxP3) and patient information, and developed the patient information model, pathological image model, and combination model. We used the area under the curves (AUC) to evaluate the machine learning models. Results: Of 78 patients, the median age was 78 (interquartile range, 48-87), 65 patients (83%) were male, 67 patients (86%) had a performance status of 0 or 1, and three patients (3.8%) treated with steroid therapy. Among all patients, the median PFS and the 365-day PFS rates were 145 days and 10.3%. The mean AUC of these models was 0.789 (range, 0.571-0.982) in the patient information model, 0.782 (range, 0.750-0.911) in the pathological image model, and 0.868 (range, 0.786-0.929) in the combination model, respectively. According to the median precision model, the median PFS was longer for the high efficacy group than the low efficacy group (the patient information model; hazard ratio (HR) 0.468, 95% confidence intervals (CI) 0.287-0.762. the pathological image model; HR 0.334, 95%CI 0.117-0.628. the combination model; HR 0.353, 95%CI 0.195-0.637). Conclusions: Using machine learning by pathological images, we could predict the efficacy of immunotherapy in SCLC. This study demonstrated the potential of machine learning to help the biomarker development in SCLC by assessing TIME. Clinical trial information: UMIN000038064 .

Nasal cytology in patients with previous SARS-CoV-2 infection: occurrence of atypical lymphocytes

SARS-CoV-2 is a new pandemic infection that affects at the beginning the upper respiratory system, and, successively, all the organisms, due to cytokine storm, with serious consequences that can reach death. The aim of this work was the observation of the nasal mucosa of enrolled 60 patients, resulting negative for two weeks to the molecular swab for SARS-CoV-2, versus the control group. Rhino-fibroscopy and nasal cytology of nasal mucosa were performed for both the investigated groups. The observation of the samples showed the occurrence of plasmablastic lymphocytes and Downey II lymphocytes type. The former type of lymphocytes was prevalent against the second one, probably because of an immunological “scar”. The rhino-fibroscopy showed a “pseudo ischemia of nasal submucosa” at pre and pericranial levels, not occurred in the control group. The occurrence of atypical lymphocytes in the nasal smear was analog to that observed in the blood peripheral smear, probably caused by mechanisms of local immune reaction and dysregulation like those observed in other virus infections. Our findings suggest that the nasal mucosa study through the nasal cytology, can represent an important predictive tool of the SARS-CoV-2 infection.

Patterns of Tumor-Infiltrating Lymphocytes Used to Distinguish Primary Cutaneous Squamous Cell Carcinomas That Metastasize

This case-control study examines the type, location, and density of tumor-infiltrating lymphocytes in adult patients with vs without metastatic cutaneous squamous cell carcinoma.

Modern PET-guided radiotherapy planning and treatment for malignant lymphoma.

Malignant lymphoma comprises a broad spectrum of diverse entities originating from different types of lymphocytes. In the last century, successive improvements of treatment possibilities have led to an continuous amelioration of patient prognosis from lethal outcome to high rates of disease control and long-term survivors. PET/CT-based imaging plays a key role in stratification of stage and treatment response. Especially for radiotherapy, an essential treatment modality for lymphoma patients, functional imaging and the reevaluation of disease activity after frontline chemotherapy has led to major improvements regarding size of treatment fields and toxicity. International expert groups like the International Lymphoma Radiation Oncology Group (ILROG) develop guidelines for the optimal use of imaging for treatment planning. The shift from uniform large-field treatment volumes to complex individual setups taking into account biological response-assessments based on functional imaging resulted in a further de-escalation of side effects and modernization of lymphoma treatment. This paper aims to summarize the use of FDG-PET-imaging for radiation therapy planning in malignant lymphoma in the context of historic and future developments, as well as associated limitations and challenges ahead. We will discuss the contemporary standard of care as recommended by international expert guidelines like the ILROG, the national comprehensive cancer network (NCCN), as well as the newly updated German S3-guidelines.

Abstract 5038: Evaluation of anti-tumor immunity in response to [177Lu]Lu-PSMA in a mouse model of prostate cancer

Abstract [177Lu]Lu-PSMA improves progression-free and overall survival in metastatic castration resistant prostate cancer. However, the role of immune stimulation by molecularly targeted radionuclide therapy (MRT) is poorly understood. The aim of this study was to evaluate the anti-tumor immune response induced by [177Lu]Lu-PSMA. The markers of immunogenic cell death (ICD), translocation of calreticulin (CRT) to the cell membrane, HMGB1 release and ATP release, were evaluated in the RM1 cell line (PSMA-negative murine prostate carcinoma) and its derivative, RM1-PGLS (stably transduced with human PSMA and SFG-EGFp/Luc), using flow cytometry, ELISA and a luminescence detection assay respectively. The in vivo biodistribution of [177Lu]Lu-PSMA in RM1-PGLS tumor-bearing C57BL/6 mice was investigated using microSPECT-CT imaging, and the in vivo efficacy of [177Lu]Lu-PSMA was tested in RM1-PGLS tumor growth inhibition studies. Vaccination/rechallenge experiments were performed to elucidate whether [177Lu]Lu-PSMA elicits ICD in vivo. The Nanostring Pan Cancer Immune Profiling Platform was used to assess changes in the tumor immune microenvironment (TIME) in response to [177Lu]Lu-PSMA. External radiation (EBRT; 137Cs γ-radiation; 6-10 Gy) was used as a comparator treatment in most experiments. We observed a dose-dependent increase in cell surface CRT following [177Lu]Lu-PSMA and EBRT at 24 and 72 h and of HMGB1 release in response to [177Lu]Lu-PSMA and EBRT at 96 and 144 h. At 24 h following [177Lu]Lu-PSMA (60 MBq) there was a significant increase in ATP release compared to untreated samples. Collectively these data indicate [177Lu]Lu-PSMA causes ICD. A high RM1-PGLS tumor:muscle uptake ratio (210 ± 59) was noted in biodistribution experiments confirming highly specific tumor accumulation of [177Lu]Lu-PSMA. In tumor growth inhibition studies the time for tumors to reach a volume of 400 mm3 was delayed in mice treated with [177Lu]Lu-PSMA (60 MBq) compared to no treatment (30 versus 21 days; P<0.01). We showed that a subcutaneous inoculum of [177Lu]Lu-PSMA (60 MBq)-treated RM1-PGLS cells prevents tumor growth in approximately 50% of cases on rechallenge with viable RM1-PGLS cells one week later. This indicates that [177Lu]Lu-PSMA induces ICD in vivo. We observed a significant reduction in most tumor infiltrating lymphocyte (TIL) types at 2 days after in vivo exposure to [177Lu]Lu-PSMA (80 MBq), followed by an increase in TILs by Day 7. The observed pattern is similar to that after EBRT (6 Gy). There was overlap in the top 10 differentially expressed genes (treatment versus no treatment) for the [177Lu]Lu-PSMA and EBRT groups. The gene showing the greatest level of upregulation at day 7 in [177Lu]Lu-PSMA-treated tumors, IDO1, is known to be involved in immune tolerance and radioresistance. In conclusion, [177Lu]Lu-PSMA induces ICD in vitro and in vivo and modulates the TIME. Citation Format: Gemma Dias, Sarah Able, Irini Skaripa-Koukelli, Rachel Anderson, Gracie Wilson, Katherine A. Vallis. Evaluation of anti-tumor immunity in response to [177Lu]Lu-PSMA in a mouse model of prostate cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5038.

Abstract 2032: Intratumoral tumor infiltrating lymphocytes is associated with cell proliferation and better survival but not with response to chemotherapy

Abstract Introduction: Abundance of tumor infiltrated lymphocytes (TILs) in the peripheral region of tumor assessed pathologically is associated with improved response to chemotherapy and better prognosis in Her2+ and triple-negative breast cancer (TNBC). Since recent progress in bioinformatics has allowed for computational deconvolution of bulk tumor, we investigated the clinical relevance of intratumoral TILs in primary breast cancer and response to neoadjuvant chemotherapy (NAC). Methods: A total of 4139 bulk tumor RNA sequencing data were analyzed for the association of high intratumoral TILs with clinicopathologic factors and biology in primary breast cancer cohorts of TCGA and SCAN-B. Total of 1719 bulk samples from three other cohorts (GSE163882, GSE25066, and GSE194040) were utilized to investigate the association between pathologic complete response rate (pCR) to neoadjuvant chemotherapy and intratumoral TILs. Results: Among several deconvolution algorithms, the sum of xCell lymphocytes was chosen to estimate intratumoral TIL since it correlated the strongest with multiple signals that represent lymphocytes. The cohorts were divided into high or low TIL tumor by median cut-off, and number of TILs in high-TIL ER+/Her2- was roughly the same as that of low-TIL TNBC. As expected, high TILs were associated with better disease specific survival in Her2+ and TNBC subtypes consistently in TCGA and SCAN-B cohorts. Immune-related gene sets were uniformly enriched to high TIL tumors regardless of subtype, and the difference in cytolytic activity by TILs were the largest in TNBC. Macrophages, dendritic cells, lymphatic and blood endothelial cells were infiltrated in TIL high tumors. Thus, estimated intra-tumor TILS showed similar immune-related characteristics with pathology-assessed TILs. However, ER+/Her2- was most strongly correlated with cell proliferation biologically, pathologically, and molecular biologically. High TIL was significantly associated with higher mutation related scores only in ER+HER2-. Unexpectedly, intratumoral TILs and all the types of lymphocytes showed low AUC for predicting pCR to NAC (AUC < 0.6). Gene expression-based scores generated by LASSO model showed low AUC in all the cohorts neither (AUC < 0.65). Conclusion: Transcriptomic signature of Intratumoral TILs is associated with cell proliferation in ER+HER2- breast cancer and better survival in HER2+ breast cancer and TNBC but is not as consistently associated with response to neoadjuvant chemotherapy as pathologically assessed TILs. Citation Format: Rongrong Wu, Masanori Oshi, Mariko Asaoka, Masayuki Nagahashi, Li Yan, Yasuo Miyoshi, Takashi Ishikawa, Kazuaki Takabe. Intratumoral tumor infiltrating lymphocytes is associated with cell proliferation and better survival but not with response to chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2032.

Regulatory roles of cytokines in T and B lymphocytes-mediated immunity in teleost fish

T and B lymphocytes (T and B cells) are immune effector cells that play critical roles in adaptive immunity and defend against external pathogens in most vertebrates, including teleost fish. In mammals, the development and immune response of T and B cells is associated with cytokines including chemokines, interferons, interleukins, lymphokines, and tumor necrosis factors during pathogenic invasion or immunization. Given that teleost fish have evolved a similar adaptive immune system to mammals with T and B cells bearing unique receptors (B-cell receptors (BCRs) and T-cell receptors (TCRs)) and that cytokines in general have been identified, whether the regulatory roles of cytokines in T and B cell-mediated immunity are evolutionarily conserved between mammalians and teleost fish is a fascinating question. Thus, the purpose of this review is to summarize the current knowledge of teleost cytokines and T and B cells as well as the regulatory roles of cytokines on these two types of lymphocytes. This may provide important information on the parallelisms and dissimilarities of the functions of cytokines in bony fish versus higher vertebrates, which may aid in the evaluation and development of adaptive immunity-based vaccines or immunostimulants.

Into the multi-omics era: Progress of T cells profiling in the context of solid organ transplantation.

T cells are the common type of lymphocyte to mediate allograft rejection, remaining long-term allograft survival impeditive. However, the heterogeneity of T cells, in terms of differentiation and activation status, the effector function, and highly diverse T cell receptors (TCRs) have thus precluded us from tracking these T cells and thereby comprehending their fate in recipients due to the limitations of traditional detection approaches. Recently, with the widespread development of single-cell techniques, the identification and characterization of T cells have been performed at single-cell resolution, which has contributed to a deeper comprehension of T cell heterogeneity by relevant detections in a single cell - such as gene expression, DNA methylation, chromatin accessibility, surface proteins, and TCR. Although these approaches can provide valuable insights into an individual cell independently, a comprehensive understanding can be obtained when applied joint analysis. Multi-omics techniques have been implemented in characterizing T cells in health and disease, including transplantation. This review focuses on the thesis, challenges, and advances in these technologies and highlights their application to the study of alloreactive T cells to improve the understanding of T cell heterogeneity in solid organ transplantation.

Single-cell RNA sequencing reveals the suppressive effect of PPP1R15A inhibitor Sephin1 in antitumor immunity

Protein phosphatase 1 regulatory subunit 15A (PPP1R15A) is an important factor in the integrated stress response (ISR) in mammals and may play a crucial role in tumorigenesis. In our studies, we found an inhibitor of PPP1R15A, Sephin1, plays a protumorigenic role in mouse tumor models. By analyzing the single-cell transcriptome data of the mouse tumor models, we found that in C57BL/6 mice, Sephin1 treatment could lead to higher levels of ISR activity and lower levels of antitumor immune activities. Specifically, Sephin1 treatment caused reductions in antitumor immune cell types and lower expression levels of cytotoxicity-related genes. In addition, Tcell receptor (TCR) repertoire analysis demonstrated that the clonal expansion of tumor-specific Tcells was inhibited by Sephin1. A special TCR+ macrophage subtype in tumor was identified to be significantly depleted upon Sephin1 treatment, implying its key antitumor role. These results suggest that PPP1R15A has the potential to be an effective target for tumor therapy.

Hemodynamic Analysis and Diagnosis Based on Multi-Deep Learning Models

This study employs nine distinct deep learning models to categorize 12,444 blood cell images and automatically extract from them relevant information with an accuracy that is beyond that achievable with traditional techniques. The work is intended to improve current methods for the assessment of human health through measurement of the distribution of four types of blood cells, namely, eosinophils, neutrophils, monocytes, and lymphocytes, known for their relationship with human body damage, inflammatory regions, and organ illnesses, in particular, and with the health of the immune system and other hazards, such as cardiovascular disease or infections, more in general. The results of the experiments show that the deep learning models can automatically extract features from the blood cell images and properly classify them with an accuracy of 98%, 97%, and 89%, respectively, with regard to the training, verification, and testing of the corresponding datasets.

The Effect of Supplementation with β-Hydroxy-β-Methylbutyric Acid (HMB) to Pregnant Sows on the Mucosal Structure, Immunolocalization of Intestinal Barrier Proteins, VIP and Leptin in the Large Intestine in their Offspring

Abstract The large intestine epithelium plays an important role in water absorption and participates in fluid, acid-base and electrolyte balance, and the removal of waste products. The large intestine is rich in microorganism-presented enzyme activity. Apart from energy supply, the colon also participates in the synthesis of trophic factors and the modulation of the immune system and the systemic inflammatory response. The current study investigated the effects of dietary HMB administration to pregnant sows on the postnatal development of the colon in their offspring, at weaning. From the 70th to the 90th day of gestation, sows received either a basal diet (n = 12) or the basal diet supplemented with HMB (n = 12) at a dose of 0.2 g/kg of body weight/day. Maternal HMB treatment increased serum IgG and glucose concentrations and decreased serum urea concentration in the piglets. Basal histomorphometric analysis of offspring large intestines showed that prenatal HMB treatment led to a reduction in the thickness of the mucosa, submucosa and both types of myenterons, as well as reduced crypt thickness. The immunoreaction performed to mark T0 lymphocytes and total T lymphocytes in the colon wall showed that prenatal HMB treatment decreased the number of both types of lymphocytes. Greater expression for cadherin was found in the colon of piglets delivered by the HMB-treated sows. The expression of both tight junction proteins (occludin and claudin-3), as well as that of leptin, was stronger in the HMB-treated group. Vasoactive intestinal peptide (VIP) expression was stronger in the submucosal plexuses in the HMB maternal treated piglets, while no changes were observed in the myenteric plexuses. The results obtained indicate that the administration of HMB to pregnant sows significantly influenced the expression of leptin, VIP and some proteins of the intestinal barrier in their offspring, with less influence on large intestine basal morphology.

The layered development of mouse B and T Cells.

Traditional models of lymphopoiesis present B and T cell development as a linear process that initiates in the fetus and continues after birth in the bone marrow and thymus, respectively. However, this view of lymphocyte development is not in accord with reports, dating back several decades, indicating that the types of lymphocytes generated before and after birth differ. In this regard, selected γδ T cells, and those that utilize the Vγ3 receptor in particular, and innate-like B-1 B cells preferentially arise during fetal blood cell development. This review synthesizes data from multiple laboratories, with an emphasis on our own work using mouse models, demonstrating that innate and conventional B and T cells emerge in hematopoietic stem cell independent and dependent waves of development that are differentially regulated. This layering of lymphocyte development has implications for understanding the composition of the adult immune system and may provide insights into the origin of various lymphocytic leukemias.

Tumor-infiltrating lymphocytes and levels of PD-L1 and BRCA protein expression may identify patients with breast cancer with a higher rate of BRCA1 mutations

Introduction. Breast cancer (BC) is a heterogeneous disease, treated as per the predictive role of immunohistoche­mistry (IHC) identifiers as estrogen/progesterone and HER2 receptor proteins. Deeper molecular classification (MC) identifies molecular subtypes according to the gene-expression profiles, with different molecular genetic alterations and biological features, present in the different subtype. An overlap between IHC and MC exists, even if somewhat incomplete. We aimed to identify the overlap between IHC and MC, and identify patients with basal-like subtype of BC. We hypothesized that the rates of tumor expression of breast cancer-related protein 1 (BRCA1), the type of tumor-infiltrating lymphocytes, and the expression of programmed death ligand 1 (PD-L1) by immune cells vary among different subtypes of BC. Material and methods. Parafin-embedded samples from 100 patients with primary invasive BC were analyzed and expression levels of estrogen and progesterone receptors, HER2 status, and Ki-67 were assessed via IHC, defining four groups – luminal A-like, luminal B-like (LumA, LumB), HER2-positive non-luminal, and triple negative (TN). The pri­mary endpoint of our study was to identify via IHC with CK5/6 and 17 basal-like subtypes of BC amongst others, and to describe specific clinicopathological features together with protein expression of BRCA1 and PD-L1 and tumor-infiltrating lymphocytes, using CD20, CD3, CD4, CD8, and FoxP3. Results. Basal-like BC were predominantly characterized as triple negative by IHC (p < 0.05) and were more frequently seen among special BC subtypes as compared to no special type (NST), with p = 0.036. Their immune response was represented mostly by high concentration of intratumoral cytotoxic CD8 (+) T-lymphocytes (p < 0.05) and stromal PD-L1-positive immune cells (p = 0.008). In these tumors, absence of expression of BRCA1 protein was more frequent (p < 0.001). Basal-like subtype of BC with absent expression of BRCA1 is associated with poorer <5-year survival (p = 0.001 and p = 0.017, respectively). Conclusions. The use of IHC can establish basal-like BC, the type of its immune response and possible dysfunction in the BRCA -gene, reflected in the lack of expression in the BRCA-related protein.

Prevalence of Anti-SARS-CoV-2 Antibodies in HIV-Positive Patients in Wroclaw, Poland—Unexpected Difference between First and Second Wave

Background: The presence and level of anti-SARS-CoV-2 antibodies in PLWH from the Lower Silesia region in Poland. Material and Methods: A total of 216 serum samples of both sexes, aged 21–77, and treated with TDF or TAF together with FTC and INSTI at two points of time. Anyone who did not experience COVID-19 symptoms. Samples were checked for the presence and levels of anti-SARS-CoV-2 antibodies regarding CD4 + T and CD8 + T cells counts, the ratio of these cells, age, sex, VL, and type of tenofovir used. Results: The average level and prevalence of anti-SARS-CoV-2 antibodies during the first wave were 65.81 IU/mL and 4.17%, while during the second wave, they were 125.98 IU/mL and 14.29%, respectively. There was a significant correlation between the number and type of lymphocytes and the presence of anti-SARS-CoV-2 antibodies. We did not find the same correlation regarding anti-SARS-CoV-2 levels. The average level of antibodies was higher during the second wave. There was no difference between the type of tenofovir used and the humoral response, as well as no correlation of anti-SARS-CoV-2 levels with age, gender, or VL. Conclusion: PLWH can have asymptomatic SARS-CoV-2 infection, which can influence the presence, but not levels, of anti-SARS-CoV-2 Ab. No correlation with type of tenofovir was observed.

B Cells Drive MHC Class I-Restricted CD4 T Cells to Induce Spontaneous Central Nervous System Autoimmunity.

Multiple sclerosis (MS) is an inflammatory, demyelinating CNS disease believed to be mediated by CD4 T cells specific for CNS self-antigens. CD8 T cells are also implicated in MS but their function is not well understood. MS lesions are heterogeneous and may reflect variation in the contribution of different types of lymphocytes. Understanding how lymphocytes with different effector functions contribute to MS is essential to develop effective therapies. We investigated how T cells expressing an MHC class I-restricted transgenic TCR specific for myelin basic protein (MBP) contribute to CNS autoimmunity using the mouse model of MS, experimental autoimmune encephalomyelitis. Virus infection triggered cytotoxic TCR-transgenic CD8 T cells to initiate acute experimental autoimmune encephalomyelitis in an IFN-γ- and perforin-dependent manner. Unexpectedly, spontaneous CNS autoimmunity developed in the TCR-transgenic mice that was accelerated by IFN-γ-deficiency. Spontaneous disease was associated with CD4 T cells that develop via endogenous TCR rearrangements but retain specificity for the MHC class I-restricted MBP epitope. The CD4 T cells produced TNF-α without other inflammatory cytokines and caused lesions with striking similarity to active MS lesions. Surprisingly, B cells were the predominant cell type that cross-presented MBP, and their depletion halted disease progression. This work provides a new model of spontaneous CNS autoimmunity with unique similarities to MS that is mediated by T cells with a distinct effector phenotype.

Clinical characteristics and short-term mortality of 102 hospitalized hemodialysis patients infected with SARS-CoV-2 omicron BA.2.2.1 variant in Shanghai, China

BackgroundThe aim of this study was to analyze clinical features and short-term mortality in hemodialysis (HD) patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) omicron BA.2.2.1 variant. MethodsIn a retrospective single-center case series, 102 consecutive hospitalized HD patients infected with the coronavirus omicron variant were assessed at Pudong Hospital in Shanghai, China, from April 6 to April 18, 2022; the final date of follow-up was May 16, 2022. Clinical, laboratory, chest CT, and treatment data were collected and analyzed. The association between these factors and all-cause mortality was studied using univariate and multivariate analyses. The relationship between lymphocyte count and short-term mortality was based on receiver operating characteristic (ROC) curve analysis. Kaplan–Meier analysis was used to assess overall survival. ResultsIn total, 102 patients were included in this study. The patients were divided into two groups: HD patients with pneumonia (N = 46) and without pneumonia (N = 56). Of the 102 patients, 12 (11.8%) died. Multivariate regression analysis revealed that all-cause mortality was correlated with lymphocyte counts and type B natriuretic peptide (BNP), C-reactive protein (CRP), and D-dimer levels (P < 0.05). The cut-off value of lymphocyte counts was 0.61 × 109/L for all-cause mortality. The overall survival rate was significantly different between HD patients with and without pneumonia (P < 0.05). ConclusionsLymphocyte counts are important for the prediction of short-term mortality in HD patients with SARS-CoV-2 infection. HD patients with lung involvement have poorer survival rates than those without lung involvement.

CD3&lt;sup&gt;+&lt;/sup&gt;CD294&lt;sup&gt;+&lt;/sup&gt;T cells of the type 2 immune response: their role in allergic inflammation

T lymphocytes type 2 immune response protect against helminths and toxins, and also contribute to the development of allergic inflammation. One of the most specific T cell surface markers T lymphocytes 2 is the CRTH2 molecule (CD294), which is an activating receptor for prostaglandin D2. The CD3+CD294+population is negligible in the peripheral blood of healthy individuals; an increase occurs in patients with allergic diseases and an autoimmune nature of the response. The aim of the study was to study the quantitative and functional characteristics Т lymphocytes type 2 immune response in patients with rhinoconjunctival symptoms (n = 248) and drug hypersensitivity (n = 184). In 68 patients with an elevated and extremely high number of CD3+CD294+cells, a detailed phenotype of this population was characterized by flow cytometry and the functional activity of the studied cell population in relation to the production of interleukin 4 and interferon γ was studied using enzyme immunoassay. The control group consisted of 34 volunteers. The relative number of CD3+CD294+cells was significantly higher in the group of patients with drug hypersensitivity – 1.6% and rhinoconjunctival symptoms 1.2% compared to the control group – 1.0%. Elevated (1.6-3.6%) and extremely high (&gt;3.6%) CD3+CD294+cell number were significantly more frequently detected in patients with drug hypersensitivity. In both groups, an increase in the number of CD3+CD294+cells were observed with severe damage to the skin. The phenotype of the population T lymphocytes type 2 CD45RA-CD3+CD294+CD2+CD5+CD7+CD27+CD28+CD57-CCR7-was determined, which corresponds to effector memory T lymphocytes. With a moderately increased relative amount of this population, T lymphocytes 2 were usually represented by T helpers 2. A pronounced increase in the population was observed due to T cytotoxic lymphocytes 2. Regardless of the predominance of the Т helper or Т cytotoxic 2 cells in patients revealed an increase in spontaneous production of interleukin 4 at a normal level of interferon. An increase in the peripheral blood T lymphocytes with CD294 expression contributes to the development, maintenance and exacerbation of allergic inflammation with the participation of IgEdependent and IgE-independent mechanisms. The CD3+CD294+cell population should be determined as an additional parameter in assessing the presence of sensitization in the basophil activation test in patients with hypersensitivity reactions. The use of this laboratory biomarker to assess the dominant type of immune inflammation will make it possible to personalize the therapy of the examined patients. Identification of pronounced deviations of indicators from the average values of a population will influence the tactics of patient management.

Studies of CD45+ and CD46+ expression on the peripheral blood lymphocyte subsets of the post-COVID patients

The SARS-CoV-2 virus can enter the cells using S1 viral spike (S) protein, not only by binding to ACE2, but also through other cellular receptors. These candidate receptors include CD46, which, like CD45, belongs to pan-leukocyte receptors and is expressed on all types of lymphocytes. In turn, SARS-CoV-2 infection is accompanied by damage to almost all compartments of the immune system, mainly T lymphocytes. The purpose of the study was to evaluate the expression levels of CD45+ and CD46+ in various subpopulations of lymphocytes in patients who had undergone SARS-CoV-2 infection.&#x0D; 72 patients who had undergone SARS-CoV-2 infection were examined. Using flow cytometry technique, we determined CD45+ and CD46+ (panleukocyte marker for lymphocyte gating), CD45+ and CD46+, CD3+ (T lymphocytes), CD45+ and CD46+, CD3+, CD4+ (helper inducers), CD45+ and CD46+, CD3+, CD8+ (cytotoxic T-lymphocytes), CD45+ and CD46+, CD3+, CD56+ (TNK cells) CD45+ and CD46+, CD3-, CD56+ (natural killers), CD45+ and CD46+, CD3-, CD19+ (B lymphocytes), CD45+ and CD46+, CD3+, CD4+, CD25+ (activated helpers, early activation of lymphocytes), CD45+ and CD46+, CD3+, HLA-DR (activated T lymphocytes late activation of lymphocytes). Our studies have shown that a decrease in CD46+ expression in T lymphocytes (CD3+) is accompanied by similar decrease of its expression in cytotoxic T lymphocytes (CD3+, CD8+), TNK (CD3+, CD56+), as well as in helpers T carrying markers of early activation (CD3+, CD4+, CD25+). At the same time, the most pronounced decrease was observed both among total T lymphocytes and cytotoxic T cells. In these patients, the expression level of CD46+ in B lymphocytes was slightly increased. Recent data suggest that there is no involvement of CD46 receptor on B lymphocytes. Our data suggest that the SARS-CoV-2 virus may affect the CD46 receptor. Such exposure may lead to promotion of the long-COVID (post-COVID) symptoms in such patients, thus requiring new approaches to correction of these disorders.

Effects of chronic heat stress on the immunophenotyping of lymphocytes in immune organs of growing pigs.

This study aimed to investigate the effects of chronic heat stress on the immunophenotyping of lymphocytes in immune organs of growing pigs. A single-factor randomized block design was used, and 15 healthy growing large white barrows (5 litters, 3 pigs/litter) with similar body weight (40.8 kg) were assigned into 3 groups (5 pigs in each group). Groups were: control group (Con, in 23 °C environmental control chamber, fed ad libitum), heat stress group (HS, in 33 °C environmental control chamber, fed ad libitum), and pair-fed group (PF, in 23 °C environmental control chamber, fed diets according to the feed intake of HS group). After a 7-d adaption, the experiment lasted for 21 d. The results showed as follows: (1) activated T cells in the thymus of HS pigs were higher than those in PF pigs (P < 0.05). Monocytes and dendritic cells in the thymus of HS pigs were significantly higher than that in Con and PF pigs (P < 0.05), while the proportions of these 2 lymphocytes in the thymus of Con pigs did not differ from PF pigs (P > 0.05). Compared with Con pigs, the proportion of CD4+ (P < 0.05) and CD8+ T cells (P < 0.10) in the thymus was increased in HS pigs, while the proportion of CD4+ and CD8+ T cells in PF pigs did not differ from Con pigs (P > 0.05). (2) Compared with Con pigs, significantly decreased T cells, increased B cells and monocytes were found in the spleen of pigs exposed to heat stress (P < 0.05); the proportions of these 3 types of lymphocytes were not significantly different between Con and PF pigs (P > 0.05). The proportions of CD4+ T cells and Treg cells in the spleen of pigs exposed to heat stress tended to be lower than those in the Con pigs (P < 0.10). (3) The proportion of lymphocytes in the tonsils of pigs exposed to heat stress did not differ from Con pigs (P > 0.05); compared with PF pigs, the proportion of Treg cells was significantly decreased in HS pigs (P < 0.05). In conclusion, chronic heat stress stimulates the development and maturation of T cells in the pig thymus toward CD4+ and CD8+ T cells and increases the proportion of monocytes and dendritic cells; under the condition of chronic heat stress, the immune response process in the spleen of pigs is enhanced, but chronic heat stress impairs the survival of CD4+ T cells in the spleen.

Association between bone mineral density and content and physical growth parameters among children and adolescents diagnosed with HIV: a cross-sectional study.

ABSTRACTBACKGROUND:During childhood and adolescence, there are significant increases in bone mineral content (BMC) and bone mineral density (BMD).OBJECTIVE:To investigate physical growth parameters associated with BMD and BMC among children and adolescents diagnosed with human immunodeficiency virus (HIV).DESIGN AND SETTING:Cross-sectional study conducted in Florianópolis, Brazil, among 63 children and adolescents (aged 8-15 years) diagnosed with HIV.METHOD:BMD, BMC and fat percentage z score were evaluated using dual X-ray absorptiometry. Age/height z score and body mass index (BMI)/age z score were obtained in accordance with international recommendations, and bone age was obtained through hand-wrist radiography. Sex, family income, information on HIV infection (T CD4+ lymphocyte count, viral load and type of antiretroviral therapy, moderate-vigorous physical activity and sedentary behavior) were used as adjustment variables in the analyses. Simple and multiple linear regression analyses were performed, with a significance level of P ≤ 0.05.RESULTS:Subtotal BMD (without the head region) was directly associated with bone age, BMI/age z score and fat percentage z score, even after adjusting for covariates. Subtotal BMC/height was directly associated with bone age, height/age z score, BMI/age z score and fat percentage z score, even after adjusting for covariates.CONCLUSION:Subtotal BMD and subtotal BMC/height were directly associated with physical growth indicators among children and adolescents diagnosed with HIV.