Peripheral Blood CD4 Research Articles

TNF-α Predicts Endothelial Function and Number of CD34+ Cells after Stimulation with G-CSF in Patients with Advanced Heart Failure.

Patients with advanced heart failure (HF) have reduced cardiac output and impaired peripheral blood flow, which diminishes endothelial shear stress and consequently flow-mediated dilatation (FMD). The aim of our study was to find out whether endothelial dysfunction is associated with the number of CD34+ cells and TNF-α levels in patients with ischemic and non-ischemic HF after stimulation with granulocyte colony-stimulating factor (G-CSF). We included 56 patients with advanced HF (LVEF < 35%). Eighteen patients (32.14%) had ischemic and 38 (67.86%) patients had non-ischemic HF. FMD of the brachial artery was performed before the patients underwent 5-day bone marrow stimulation with daily subcutaneous injections of G-CSF (5 μg/kg bid). On the fifth day peripheral blood CD34+ cell count was measured. No statistically significant differences were found between the patient groups in NT-proBNP levels ((1575 (425–2439) vs. 1273 (225–2239)) pg/mL; p = 0.40), peripheral blood CD34+ cell count ((67.54 ± 102.32 vs. 89.76 ± 71.21) × 106; p = 0.32), TNF-α ((8.72 ± 10.30 vs. 4.96 ± 6.16) ng/mL; p = 0.13) and FMD (6.7 ± 5.4 vs. 7.2 ± 5.9%; p = 0.76). In a linear regression model, only FMD (p = 0.001) and TNF-α (p = 0.003) emerged as statistically significant predictors of CD34+ cells counts. Our study suggests that TNF-α is a good predictor of impaired endothelial function and of CD34+ cells mobilization after G-CSF stimulation in patients with advanced HF of ischemic and non-ischemic origin.

Evaluation of CD34+ Cell Count at Different Time Points Following Plerixafor Administration in Autologous Hematopoietic Stem Cell Transplantation

Background: In apheresis, collecting an adequate number of CD34+ cells is required for successful autologous hematopoietic stem cell transplantation (auto-HSCT) procedure. It is difficult to harvest a sufficient number of stem cells in certain patients due to their old age and history of intensive chemotherapy. Plerixafor could mobilize stem cells and facilitate peripheral blood hematopoietic stem cell collection. However, not enough information is available on the appropriate time intervals from plerixafor administration to apheresis. Objectives: In this study, we aimed at evaluating the level of peripheral blood CD34+ cells at plerixafor administration time and every three hours to identify the peak time of circulating CD34+ cells. Methods: Circulating CD34+ cells were enumerated by flow cytometry on day 4 post mobilization. Plerixafor was administered to patients with poor mobilization based on the count of peripheral blood hematopoietic stem cells. The number of circulating CD34+ cells was evaluated before and 3, 6, 9, and 12 hours after plerixafor administration to assess the time it takes for stem cells to reach their peak level. Results: The highest level of stem cell concentration was found in 9 hours after plerixafor administration with an increasing trend. A statistically significant relationship was also observed between factors including platelet count on the first day of GCSF injection and the day of stem cell infusion, leukocyte count on admission, and basal levels of CD34+ cells in peripheral blood and the amount of harvested stem cells. Conclusions: We demonstrated that plerixafor causes an incremental trend in CD34+ cells mobilization, reaching its peak after 9 hours. Further research should be performed to provide insights into graft cells’ population and hematologic and immunological recovery.

Apheresis of Deceased Donors as a New Source of Mobilized Peripheral Blood Hematopoietic Stem Cells for Transplant Tolerance.

Solid organ transplantation is the therapy of choice for many patients with end-stage organ failure; however, recipients must remain on lifelong immunosuppression, leaving them susceptible to infections and cancer. The study of transplant tolerance to prolong graft survival in the absence of immunosuppression has been restricted to recipients of living donor allografts; however, deceased donors significantly outnumber living donors. Mobilization of hematopoietic stem cells (HSCs) from the bone marrow to peripheral blood (PB) could allow PB-HSCs to be used to induce tolerance in deceased donor kidney recipients; however, a major concern is the well-known concomitant mobilization of immune cells into the liver. We mobilized HSCs to the PD using a protocol of 2 doses of granulocyte colony-stimulating factor and 1 dose of plerixafor, followed by the collection of mobilized cells via apheresis in 3 deceased donors. The physiological, laboratory, and radiographic parameters were monitored throughout the procedure. Longitudinal biopsies were performed to assess the potential for ectopic liver mobilization. The use of both agents led to the successful mobilization of peripheral blood CD34+ cells, demonstrating the potential for use in transplant tolerance protocols. Increased immune cell trafficking into the liver was not observed, and apheresis of mobilized cells resulted in a uniform decrease in all liver leukocyte subsets. HSCs can be mobilized and collected from the PB of brain-dead donors. This new approach may facilitate the dissemination of immune tolerance trials beyond living-donor kidney transplantation to deceased-donor transplantation, without sacrificing the transplantability of the liver.

SARS-CoV-2 Spike Does Not Possess Intrinsic Superantigen-like Inflammatory Activity

Multisystem inflammatory syndrome in children (MIS-C) is a rare hyperinflammatory disease occurring several weeks after SARS-CoV-2 infection. The clinical similarities between MIS-C and the toxic shock syndrome, together with the preferential expansion of T cells with a T-cell receptor variable β chain (TCRVβ) skewing, suggested a superantigen theory of MIS-C. For instance, recent in silico modelling evidenced the presence of a highly conserved motif within SARS-CoV-2 spike protein similar in structure to the superantigenic fragment of staphylococcal enterotoxin B (SEB). However, experimental data on the superantigenic activity of the SARS-CoV-2 spike have not yet been provided. Here, we assessed the superantigenic activity of the SARS-CoV-2 spike by analysing inflammatory cytokine production in both Jurkat cells and the peripheral blood CD4+ T cells stimulated with the SARS-CoV-2 spike or SEB as a control. We found that, unlike SEB, the SARS-CoV-2 spike does not exhibit an intrinsic superantigen-like activity.

Levels of Peripheral Th17 Cells and Th17-Related Cytokines in Patients with Ankylosing Spondylitis: A Meta-analysis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease. Several proinflammatory cytokines produced by T helper 17 (Th17) cells are involved in the pathogenesis of AS. We performed a meta-analysis to determine the levels of Th17 cells and serum Th17-associated cytokines in patients with AS. We determined the levels of Th17 cells and Th17 cytokines in patients with AS using data extracted from published articles retrieved from the PubMed, Embase, Web of Science, Cochrane Library, MEDLINE, Web of Knowledge, Clinical Trials.gov, and FDA.gov. The effect estimates were pooled using a random-effects model. The review protocols were registered on PROSPERO (reference: CRD42021255741) and followed the PRISMA guideline. This meta-analysis included 138 studies. Compared to healthy controls (HCs), patients with AS had a higher proportion of Th17 cells (standardized mean difference [SMD] 2.23, 95% confidence interval [CI] 1.78-2.68; p < 0.001) and levels of proinflammatory cytokines, such as interleukin (IL)-17 (SMD 2.04, 95% CI 1.70-2.38; p < 0.001), IL-21 (SMD 1.77, 95% CI 0.95-2.59; p < 0.001), and IL-23 (SMD 1.11, 95% CI 0.78-1.44; p < 0.001). The subgroup analysis showed higher levels of IL-17+ Th17 cells among peripheral blood mononuclear cells (PBMCs) and CD4+ T cells in patients with AS compared to HCs (SMD 2.26, 95% CI 1.58-2.94 [p < 0.001] and SMD 1.61, 95% CI 0.55-2.67 [p = 0.003], respectively). Patients with AS had higher levels of CD4+IL-17+IFN-γ- Th17 in PBMCs and of CD4+CCR6+CCR4+Th17 in CD4+ T cells compared to HCs (SMD 1.85, 95% CI 1.06-2.64 [p < 0.001] and SMD 7.72, 95% CI 6.55-8.89 [p < 0.001], respectively). No significant differences were observed in the proportions of CD4+IL-17+IFN-γ- Th17 in CD4+ T cells and CD4+CCR6+CCR4+ Th17 in PBMCs (SMD - 0.11, 95% CI - 0.61 to 0.38 [p = 0.650] and SMD 1.32, 95% CI - 0.54 to 3.19 [p = 0.165], respectively). In addition, compared to stable AS, the levels of Th17 cells and IL-17 and IL-23 were significantly higher in active AS (SMD 1.58, 95% CI 0.30-2.85 [p = 0.016], SMD 3.52, 95% CI 0.72-6.33 [p = 0.014], and SMD 5.10, 95% CI 1.83-8.36 [p = 0.002], respectively). The levels of Th17 cells and serum IL-17, IL-21, and IL-23 were higher in patients with AS than in HCs and, compared with stable AS, they increased more significantly in active AS. These results suggest that Th17 cells and Th17-related cytokines play major roles in AS pathogenesis and are an important target for treatment.

A clinical study of mycophenolate mofetil combined with low-dose steroids in the management of pediatric systemic lupus erythematosus

Purpose: To investigate the efficacy and safety of mycophenolate mofetil (MMF) combined with lowdose steroids in the treatment of pediatric systemic lupus erythematosus (pSLE).Methods: A total of 76 children were diagnosed and admitted with SLE, lupus nephritis (LN) and type IV diffuse proliferative glomerulonephritis at Hainan Women and Children’s Medical Center, Haikou, China from March 2017 to December 2018, had their clinical data analyzed retrospectively. Among them, 38 children received methylprednisolone pulse combined with MMF and intermittent oral low-dose glucocorticoids (GC), labelled MMF group, while the remaining 38 children, which served as control group, were treated with oral GC and transitional reduction. Pertinent biochemical parameters were evaluatedResults: Compared with control group, MMF group showed a notably lower level of erythrocyte sedimentation rate (ESR), a higher level of complement C3, lower level of serum creatinine (Scr) and 24-h urine protein level 6 months after treatment (p &lt; 0.05). Albumin level was higher in MMF group at 6 months and 12 months after treatment than in the control group. Compared to control group, the SLEDAI score in MMF group was significantly lower at 6 months and 12 months after treatment (p &lt; 0.05). Body mass index, triglyceride, fasting blood glucose and intraocular pressure levels in the MMF group were significantly lower than those in the control group (p &lt; 0.05). Post-treatment, peripheral blood CD3+ and CD4+ T lymphocytes, CD4+/CD8+ ratio and NK cell levels in the two groups were significantly increased, while CD8+ T lymphocyte level declined.Conclusion: MMF combined with low-dose methylprednisolone controls symptoms early and mitigates renal injury in the treatment of pSLE. It is also safe, and effectively regulates the patient's cellular immune function.

Correlation between peripheral blood lymphocyte subpopulations and primary systemic lupus erythematosus.

This study explored the correlation between peripheral blood CD3＋, CD3＋/CD4＋, CD3+/CD8+, CD4＋/CD8＋, CD3−/CD16+ CD56+, and CD3−CD19+ and disease activity of different subtypes of systemic lupus erythematosus (SLE). The percentages of CD3+, CD3+/CD4+, CD3+/CD8+, CD4+/CD8+, CD3−/CD16+ CD56+, and CD3−CD19+ in the peripheral blood of patients (n = 80) classified into lupus nephritis, blood involvement, and joint involvement and SLE in different active stages were detected by flow cytometry. Their correlations with baseline clinical experimental indicators of SLE patients’ SLE disease activity index score (SLEDAI) and complement C3 were analyzed. The results showed that CD3+, CD3+/CD4+, and CD3+/CD8+ at baseline level were negatively correlated with SLEDAI scores. These were positively correlated with C3. In conclusion, T-lymphocyte subpopulations are closely related to SLE activity and can be used as reference indicators to evaluate the SLE activity.

Where do T cell subsets stand in SARS-CoV-2 infection: an update.

An outbreak of coronavirus disease 2019 (COVID-19) emerged in China in December 2019 and spread so rapidly all around the globe. It’s continued and spreading more dangerously in India and Brazil with higher mortality rate. Understanding of the pathophysiology of COVID-19 depends on unraveling of interactional mechanism of SARS-CoV-2 and human immune response. The immune response is a complex process, which can be better understood by understanding the immunological response and pathological mechanisms of COVID-19, which will provide new treatments, increase treatment efficacy, and decrease mortality associated with the disease. In this review we present a amalgamate viewpoint based on the current available knowledge on COVID-19 which includes entry of the virus and multiplication of virus, its pathological effects on the cellular level, immunological reaction, systemic and organ presentation. T cells play a crucial role in controlling and clearing viral infections. Several studies have now shown that the severity of the COVID-19 disease is inversely correlated with the magnitude of the T cell response. Understanding SARS-CoV-2 T cell responses is of high interest because T cells are attractive vaccine targets and could help reduce COVID-19 severity. Even though there is a significant amount of literature regarding SARS-CoV-2, there are still very few studies focused on understanding the T cell response to this novel virus. Nevertheless, a majority of these studies focused on peripheral blood CD4+ and CD8+ T cells that were specific for viruses. The focus of this review is on different subtypes of T cell responses in COVID-19 patients, Th17, follicular helper T (TFH), regulatory T (Treg) cells, and less classical, invariant T cell populations, such as δγ T cells and mucosal-associated invariant T (MAIT) cells etc that could influence disease outcome.

Clinical Significance of Negative Costimulatory Molecule PD-1/PD-L1 on Peripheral Blood Regulatory T Cell Levels among Patients with Pulmonary Tuberculosis.

Objective This study aimed to investigate the expression and clinical significance of negative costimulatory molecules programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) on CD4+CD25+CD127low regulatory T cells (Tregs) in peripheral blood of patients with active pulmonary tuberculosis (TB). Methods A total of 30 patients with active pulmonary TB and 20 healthy controls were enrolled. The proportions of peripheral blood CD4+CD25+CD127low Tregs and the expression of PD-1 and PD-L1 on CD4+CD25+CD127low Tregs were detected among active pulmonary TB patients using flow cytometry. The associations of proportions of CD4+CD25+CD127low Tregs with the demographic and clinical characteristics of active pulmonary TB patients were evaluated, and the correlation between PD-1/PD-L1 expression and proportions of peripheral blood CD4+CD25+CD127low Tregs was examined among patients with active pulmonary TB using Pearson correlation analysis. Results Flow cytometry detected a significantly higher proportion of peripheral blood CD4+CD25+CD127low Tregs in the TB group than in the control group (9.14% ± 2.66% vs. 6.39% ± 1.73%; t = 4.067, P < 0.001), and a higher proportion of peripheral blood CD4+CD25+CD127low Tregs among active pulmonary TB patients with a positive anti-M. tuberculosis antibody than in those with a negative antibody (Figure 2(a)); however, there were no gender, M. tuberculosis culture, tuberculin test, CT examination, or sputum smear test-specific proportions of CD4+CD25+CD127low Tregs among patients with active pulmonary TB. The PD-1 (6.13% ± 3.53% vs. 24.78% ± 7.73%, P < 0.05) and PD-L1 levels (2.97% ± 2.00% vs. 9.23% ± 5.76%, P < 0.05) were lower on peripheral blood CD4+CD25+CD127low Tregs among the TB group than in the control group. In addition, Pearson correlation analysis revealed a positive correlation between PD-1 and PD-L1 expression on peripheral blood CD4+CD25+CD127low Tregs among patients with active pulmonary TB (r = 0.435, P=0.016) and a negative correlation between the proportion of peripheral blood CD4+CD25+CD127low Tregs and PD-1 (r = ‒0.344, P=0.024) and PD-L1 expression among patients with active pulmonary TB (r = ‒0.310, P=0.043). Conclusion The proportion of CD4+CD25+CD127low Tregs is higher in patients with active pulmonary TB than in healthy controls, and the negative costimulatory signal PD-1/PD-L1 expression is downregulated among active pulmonary TB patients. Our findings provide insights into the illustration of pathogenic mechanisms and immunotherapy of active pulmonary TB.

Antimicrobial and immunomodulatory effects of tannic acid supplementation in broilers infected with Salmonella Typhimurium

Infection by Salmonella Typhimurium, a food-borne pathogen, can reduce the poultry production efficiency. The objective of this study was to investigate the effects of tannic acid (TA) supplementation on growth performance, Salmonella colonization, gut barrier integrity, serum endotoxin levels, antioxidant capacity, gut health, and immune function in broilers infected with the Salmonella enterica serovar Typhimurium nalidixic acid resistant strain (STNR). A total of 546 one-day-old broilers were arbitrarily allocated into 6 treatments including 1) Sham-challenged control (SCC; birds fed a basal diet and administrated peptone water); 2) Challenged control (CC; birds fed a basal diet and inoculated with 108 STNR); 3) Tannic acid 0.25 (TA0.25; CC + 0.25 g/kg TA); 4) TA0.5 (CC + 0.5 g/kg TA); 5) TA1 (CC + 1 g/kg TA); and 6) TA2 (CC + 2 g/kg TA). On D 7, supplemental TA linearly reduced STNR colonization in the ceca (P < 0.01), and TA1 and TA2 group had significantly lower reduced STNR colonization in the ceca (P < 0.01). On D 7 to 21, average daily gain tended to be linearly increased by supplemental TA (P = 0.097). The serum endotoxin levels were quadratically decreased by supplemental TA on D 21 (P < 0.05). Supplemental TA quadratically increased ileal villus height (VH; P < 0.05), and the TA0.25 group had higher ileal VH compared to the CC group (P < 0.05). Supplemental TA linearly increased percentage of peripheral blood CD8+ T cells on D 18 (P < 0.01). The TA0.5 group had significantly lower lymphocyte numbers compared to the CC groups (P < 0.05). The abundance of monocytes linearly increased with TA supplementation (P < 0.01). Therefore, broilers fed TA had reduced STNR colonization, increased growth performance, decreased serum endotoxin levels, enhanced gut health in the broilers, and stimulated the immune system in broilers infected with STNR. Supplementation of TA (1–2 g/kg) enhanced growth performance and gut health via antimicrobial and immunostimulatory effects in broilers infected with STNR.

A novel mechanism of regulation of the oncogenic transcription factor GLI3 by toll-like receptor signaling.

The transcription factor GLI3 is a member of the GLI family and has been shown to be regulated by canonical hedgehog (HH) signaling through smoothened (SMO). Little is known about SMO-independent regulation of GLI3. Here, we identify TLR signaling as a novel pathway regulating GLI3 expression. We show that GLI3 expression is induced by LPS/TLR4 in human monocyte cell lines and peripheral blood CD14+ cells. Further analysis identified TRIF, but not MyD88, signaling as the adapter used by TLR4 to regulate GLI3. Using pharmacological and genetic tools, we identified IRF3 as the transcription factor regulating GLI3 downstream of TRIF. Furthermore, using additional TLR ligands that signal through TRIF such as the TLR4 ligand, MPLA and the TLR3 ligand, Poly(I:C), we confirm the role of TRIF-IRF3 in the regulation of GLI3. We found that IRF3 directly binds to the GLI3 promoter region and this binding was increased upon stimulation of TRIF-IRF3 with Poly(I:C). Furthermore, using Irf3−/− MEFs, we found that Poly(I:C) stimulation no longer induced GLI3 expression. Finally, using macrophages from mice lacking Gli3 expression in myeloid cells (M-Gli3−/−), we found that in the absence of Gli3, LPS stimulated macrophages secrete less CCL2 and TNF-α compared with macrophages from wild-type (WT) mice. Taken together, these results identify a novel TLR-TRIF-IRF3 pathway that regulates the expression of GLI3 that regulates inflammatory cytokines and expands our understanding of the non-canonical signaling pathways involved in the regulation of GLI transcription factors.

Transmembrane Protein ANTXR1 Regulates γ-Globin Expression by Targeting the Wnt/β-Catenin Signaling Pathway.

Reactivation of fetal hemoglobin (HbF, α2γ2) alleviates clinical symptoms in patients with β-thalassemia and sickle cell disease, although the regulatory mechanisms of γ-globin expression have not yet been fully elucidated. Recent studies found that interfering with the expression of the membrane protein ANTXR1 gene upregulated γ-globin levels. However, the exact mechanism by which ANTXR1 regulates γ-globin levels remains unclear. Our study showed that overexpression and knockdown of ANTXR1 in K562, cord blood CD34+, and HUDEP-2 cells decreased and increased γ-globin expression, respectively. ANTXR1 regulates the reactivation of fetal hemoglobin (HbF, α2γ2) in K562, cord blood CD34+, and adult peripheral blood CD34+ cells through interaction with LRP6 to promote the nuclear entry of β-catenin and activate the Wnt/β-catenin signaling pathway. The overexpression or knockdown of ANTXR1 on γ-globin and Wnt/β-catenin signaling in K562 cells was reversed by the inhibitor XAV939 and the activator LiCl, respectively, where XAV939 inhibits the transcription of β-catenin in the Wnt pathway, but LiCl inhibits GSK3-β. We also showed that the binding ability of the rank4 site in the transcriptional regulatory region of the SOX6 gene to c-Jun was significantly increased after overexpression of ANTXR1 in K562 cells. SOX6 protein expression was increased significantly after overexpression of the c-Jun gene, indicating that the transcription factor c-Jun initiated the transcription of SOX6, thereby silencing γ-globin. Our findings may provide a new intervention target for the treatment of β-hemoglobinopathies.

LB884 Integrated transcriptome and trajectory analysis of cutaneous T-cell lymphoma identifies putative precancer populations

Cutaneous T-cell lymphoma (CTCL) incidence increases with age, and blood involvement portends a worse prognosis. To advance our understanding of CTCL development and identify potential therapeutic targets, we performed integrative analyses of paired single-cell RNA and TCR sequencing of peripheral blood CD4+ T-cells from CTCL patients to reveal disease unifying features. The malignant CD4+ T-cells of CTCL show highly diverse transcriptomic profiles across patients, with most displaying a mature Th2 differentiation and T-cell exhaustion phenotype.

Effect of aging on immune cells in male HIV-infected and -uninfected healthy individuals.

HIV induces immunologic dysfunction in T cells of infected individuals. However, the impact of aging on T cell phenotypes in HIV-infected individuals receiving antiretroviral therapy (ART) has not been fully delineated. We evaluated the relationship between aging and the expression of immune activation and exhaustion markers on CD8 + T cells of age-matched HIV-infected and -uninfected male participants. Levels of immune activation and exhaustion markers on peripheral blood CD8 + T cells of HIV-infected and -uninfected participants were examined. 110 HIV-infected aviremic male participants receiving ART and 146 HIV-uninfected male participants were studied. The levels of TIGIT, PD-1, CD38, and CD226 on CD8 + T cells of the study participants were determined by flow cytometry. The level of TIGIT on CD8 + T cells was higher in aviremic HIV-infected compared to uninfected participants ( P < 0.0001). In contrast, no significant differences were found in the levels of PD-1 and CD38 on CD8 + T cells between the two groups. Statistically significant correlations were observed between age and the levels of TIGIT + and CD38 + CD8 + T cells in both groups; however, no correlation was found between age and the level of PD-1 + CD8 + T cells in HIV-infected participants. Age-stratification of HIV-infected and -uninfected groups did not show any significant differences in the level of PD-1 expression on CD8 + T cells. The findings of our study highlight the role of aging in the expression of immune markers on CD8 + T cells and have important implications for therapies that target immune checkpoints in HIV-infected individuals.

Accurate liquid biopsy for the diagnosis of non-alcoholic steatohepatitis and liver fibrosis

ObjectiveClinical diagnosis and approval of new medications for non-alcoholic steatohepatitis (NASH) require invasive liver biopsies. The aim of our study was to identify non-invasive biomarkers of NASH and/or liver fibrosis.DesignThis...

T helper cell subsets and related target cells in acute COVID-19

Current review presents a brief overview of the immune system dysregulation during acute COVID-19 and illustrates the main alterations in peripheral blood CD4+ T-cell (Th) subsets as well as related target cells. Effects of dendritic cell dysfunction induced by SARS-CoV-2 exhibited decreased expression of cell-surface HLA-DR, CCR7 as well as co-stimulatory molecules CD80 and CD86, suggesting reduced antigen presentation, migratory and activation capacities of peripheral blood dendritic cells. SARS-CoV-2-specific Th cells could be detected as early as days 24 post-symptom onset, whereas the prolonged lack of SARS-CoV-2-specific Th cells was associated with severe and/or poor COVID-19 outcome. Firstly, in acute COVID-19 the frequency of Th1 cell was comparable with control levels, but several studies have reported about upregulated inhibitory immune checkpoint receptors and exhaustion-associated molecules (TIM3, PD-1, BTLA, TIGIT etc.) on circulating CD8+ T-cells and NK-cells, whereas the macrophage count was increased in bronchoalveolar lavage (BAL) samples. Next, type 2 immune responses are mediated mainly by Th2 cells, and several studies have revealed a skewing towards dominance of Th2 cell subset in peripheral blood samples from patients with acute COVID-19. Furthermore, the decrease of circulating main Th2 target cells basophiles and eosinophils were associated with severe COVID-19, whereas the lung tissue was enriched with mast cells and relevant mediators released during degranulation. Moreover, the frequency of peripheral blood Th17 cells was closely linked to COVID-19 severity, so that low level of Th17 cells was observed in patients with severe COVID-19, but in BAL the relative number of Th17 cells as well as the concentrations of relevant effector cytokines were dramatically increased. It was shown that severe COVID-19 patients vs. healthy control had higher relative numbers of neutrophils if compared, and the majority of patients with COVID-19 had increased frequency and absolute number of immature neutrophils with altered ROS production. Finally, the frequency of Tfh cells was decreased during acute COVID-19 infection. Elevated count of activated Tfh were found as well as the alterations in Tfh cell subsets characterized by decreased regulatory Tfh1 cell and increased pro-inflammatory Tfh2 as well as Tfh17 cell subsets were revealed. Descriptions of peripheral blood B cells during an acute SARS-CoV-2 infection werev reported as relative B cell lymphopenia with decreased frequency of nave and memory B cell subsets, as well as increased level of CD27hiCD38hiCD24 plasma cell precursors and atypical CD21low B cells. Thus, the emerging evidence suggests that functional alterations occur in all Th cell subsets being linked with loss-of-functions of main Th cell subsets target cells. Furthermore, recovered individuals could suffer from long-term immune dysregulation and other persistent symptoms lasting for many months even after SARS-CoV-2 elimination, a condition referred to as post-acute COVID-19 syndrome.

Long-term Effects of Regular Whole Blood Donation on Peripheral Blood CD34+ Cells Population with using Leukoreduction Filters.

Background & Objective:Trapped cell population in leukoreduction filters (LRFs) contains such a significant number of CD34+ hematopoietic stem cells that can be recovered to be used in research studies. Methods:Samples (n=20) were obtained from 10 first-time donors and 10 regular blood donors with more than 30 times blood donation. After separating leukocytes from LRFs by backflushing, total leukocyte number and differential count were determined in both groups using an automated haemocytometer. Then cell viability and CD34+ cell quantification were assessed using 7- amino-actinomycin D and fluorescent-labeled monoclonal antibodies using flow cytometry, respectively.Results:Total leukocyte count was 665±164.92×106 in the first-time blood donors and 883±233.89×106 in the regular donors, which were not significantly different (P=0.08). While the number of CD34+ cells was significantly reduced in the regular donors compared to the first-time donors (0.58±0.20×106/µL vs. 0.36±0.22×106/µL; P=0.034). There was no significant difference in terms of absolute neutrophil count (10.58±3.66×06 vs. 13.17±6.45×106/µL; P=0.349), lymphocytes (7.75±3.11×106 vs. 10.38±3.77×106 /µL; P=0.917), and monocytes (2.31±0.88×106 vs. 2.59±1.09×106/µL; P=0.591) between the first-time and regular donor groups, respectively. Based on the correlation coefficients, the participants’ age had no significant effect on these variables. Conclusion:The results of this study depicted that regular blood donation reduces the number of CD34+ cells in the peripheral blood (PB) of regular donors while it has no significant effect on the ratio of myeloid to lymphoid cells of the two groups.

Peripheral blood CD3+ T-cell gene expression biomarkers correlate with clinical frailty in patients with haematological malignancies.

Older patients with cancer often receive treatment regimens based on their age without considering other objective factors that may influence outcomes. Assessment of frailty can identify older patients who are robust and therefore more likely to benefit from intensive treatment, or conversely, frail and might instead be offered alternative approaches. However, such assessment requires specialised training and dedicated clinical resources. Alternative quantitative biomarkers associated with frailty are lacking. Here, we asked if expression signatures of 74 immune cell, ageing, and senescence-related messenger RNAs in purified peripheral blood T cells could identify associations with clinical frailty in patients with haematological malignancies. We studied 69 patients between the ages of 36 and 92 years (median 76 years) with leukaemia, lymphoma, or multiple myeloma, across two institutions. Expression of four genes (aryl hydrocarbon receptor [AHR], CD27, CD28, and interleukin-2 receptor subunit alpha [IL2RA; CD25]) in T cells was associated with frailty, independent of age. An expression-based regression model had 76% sensitivity and 90% specificity to assign a patient as robust. These data identify measurable peripheral blood correlates of clinical frailty and suggest biomarkers for future prospective assessment.

Analysis on the Efficacy of Bronchial Artery Chemoembolization Combined with 125I Seed Implantation in the Therapy of Advanced Non-Small-Cell Lung Cancer Based on the Medical Database.

Objective To investigate the use and the efficacy of bronchial artery chemoembolization combined with 125I seed implantation in advanced non-small-cell lung cancer (NSCLC) therapy based on the medical database. Methods A total of 102 patients with advanced NSCLC were randomly divided into two groups. The control group was treated with 125I seed implantation, and the observation group was treated with bronchial artery chemoembolization (BACE) combined with 125I seed implantation based on medical database. The clinical efficacy, carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), glycan antigen 125 (CA125), peripheral blood CD3+, CD8+, CD4+/CD8+ T cells, insulin-like growth factor type 1 receptor (IGF-1R), S100 calcium-binding protein A2 (S100A2), long-term efficacy (time to disease progression, six-month survival rate, and one-year survival rate), and safety were then analyzed. Result The disease remission rate in the observation group was 62.75%, which was higher than that in the control group (41.18%). After 1 month and 3 months of treatment, the levels of serum CYFRA21-1, CEA, CA125, and IGF-1R were lower, while serum S100A2 was higher in the observation group than in the control group (P < 0.05). For safety assessment, we found that the incidences of neutropenia, thrombocytopenia, and gastrointestinal reactions had no statistical differences between two groups. The time to disease progression in the observation group was 129.85 d longer than that in the control group, 89.74 d, and the six-month survival rate and 1-year survival rate were higher in the observation group relative to the control group. Conclusion Medical database-based BACE combined with 125I seed implantation in the therapy of advanced NSCLC patients has definite efficacy with certain safety, which can enhance antitumor effect and prolong survival rate in advanced NSCLC patients.

Blood CD4+CD25+ T regulatory cells constitute a potential predictive marker of subsequent miscarriage in unexplained recurrent pregnancy loss

The aim of this study was to investigate the relationship between pre-pregnancy blood immune status and unexplained recurrent pregnancy loss (URPL), and to evaluate the predictive value of pre-pregnancy blood Treg levels for subsequent miscarriage in patients with URPL. We retrospectively analyzed 76 women who had experienced two or more miscarriages before 24 weeks of gestation for no obvious reason, and 74 women who had achieved live births as controls. Flow-cytometric analysis of peripheral blood CD4 + T cells, CD8 + T cells, NK cells, NKT cells, B cells, NK cell subpopulations (including CD56bright NK cells, CD56dim NK cells, CD56dimCD16+ NK cells, and CD56brightCD16− NK cells) was executed in the luteal phase of women in the URPL and control groups. When we reviewed and analyzed reproductive outcomes in URPL patients, we found that blood Tregs were significantly lower in the URPL group than in the controls (1.89% ± 0.61% vs. 2.15% ± 0.58%, P < 0.01) during the luteal phase pre-pregnancy. However, we discerned no differences among blood CD4+T cells, CD8+T cells, B cells, NKT cells, or NK cells, NK subpopulations (CD56bright NKs, CD56dim NKs, CD56dimCD16+ NKs, or CD56brightCD16− NKs) between the two groups. By implementing receiver operating characteristic (ROC) curve analysis to determine whether Treg levels predicted subsequent miscarriages, we found that the area under the ROC curves was 0.714, and that the cutoff value was 1.35, with a sensitivity of 0.556 and specificity of 0.923. Based on the cutoff value, we divided pregnant URPL patients into two groups, demonstrating that the subsequent miscarriage rates in the low-Treg level group (<1.35%) were significantly higher than those in the normal-Treg level group (>1.35%) (71.43% vs. 14.29%, P < 0.01). ConclusionThe pre-pregnancy blood Treg level was a potential marker that predicted subsequent miscarriage in women with URPL.