Cell-mediated Immunity In Patients Research Articles

Programmed cell death ligand 1 expression on monocytes is inversely correlated with tumour response to preoperative chemoradiotherapy for locally advanced rectal cancer.

The clinical efficacy of chemoradiotherapy (CRT) is largely dependent on host immune status. The aim of this study was to identify possible markers expressed on circulating mononuclear cells to predict tumour response in patients with locally advanced rectal cancer (LARC). Peripheral blood samples were obtained from 47 patients diagnosed with LARC before and after CRT. The numbers of lymphocytes and monocyte subsets were analysed using flow cytometry. Based on clinical and pathological findings, patients were classified as high or low responders. Lymphocyte counts were markedly decreased after CRT. Total numbers of lymphocytes (p=0.030) and CD4(+) T cells (p=0.041) in post-CRT samples were significantly lower in low responders than in high responders. In contrast, monocyte counts were not reduced and the number of CD14dim (+) CD16(+) nonclassical (patrolling) monocytes were somewhat increased after CRT (p=0.050). Moreover, the ratios of programmed cell death ligand 1 (PD-L1) (+) cells on patrolling monocytes before and after CRT were significantly higher in low responders than in high responders (p=0.0046, p=0.0006). The same trend was observed for classical and intermediate monocytes. The expression of PD-L1 on patrolling monocytes before CRT correlated inversely with the number of T cells and natural killer (NK) cells after CRT. PD-L1(+) ratio in patrolling monocytes was an independent predictor for response to CRT. Programmed cell death ligand 1 (PD-L1) expression on patrolling monocytes suppresses cell-mediated immunity in patients receiving CRT which could be related to tumour response, and may be a useful biomarker for decision-making in the management of patients with LARC.

Preserved SARS-CoV-2 Vaccine Cell-Mediated Immunogenicity in Patients With Inflammatory Bowel Disease on Immune-Modulating Therapies.

Immune-modulating medications for inflammatory bowel diseases (IBDs) have been associated with suboptimal vaccine responses. There are conflicting data with SARS-CoV-2 vaccination. We therefore assessed SARS-CoV-2 vaccine immunogenicity at 2 weeks after second mRNA vaccination in 29 patients with IBD compared with 12 normal healthy donors. We observed reduced humoral immunity in patients with IBD on infliximab. However, we observed no difference in humoral and cell-mediated immunity in patients with IBD on infliximab with a thiopurine or vedolizumab compared with normal healthy donors. This is the first study to demonstrate comparable cell-mediated immunity with SARS-CoV-2 vaccination in patients with IBD treated with different immune-modulating medications.

Some features of cell-mediated immunity in patients with breast cancer undergoing breast implant reconstruction

<h3></h3> Протезирование молочной железы после мастэктомии по поводу рака молочной железы (РМЖ) является важным реабилитационным этапом при этом заболевании. В осложнениях, развивающихся при имплантации протезов, может играть роль состояние иммунной системы больных. В работе исследованы показатели клеточного иммунитета в раневой и аксиллярной жидкости 46 больных РМЖ в течение 7 дней после имплантации текстурированного имплантата (ТИ) или полиуретанового имплантата (ПУИ). В периферической крови, а также в раневом отделяемом из полости с различными имплантатами с использованием метода проточной цитометрии определяли относительное содержание популяций и субпопуляций иммунокомпетентных клеток. Сравнение полученных результатов аксиллярной жидкости с соответствующими параметрами в циркуляторном русле выявило, что изменения в клеточных показателях при использовании имплантатов обоих типов в основном схожи. Увеличение содержания цитотоксических CD8⁺-лимфоцитов, NK-лимфоцитов и NKT-лимфоцитов указывает на то, что уже в первую неделю послеоперационного периода закладывается базис для повышенного фиброгенеза при использовании ТИ. В целом в отношении локального иммунитета больных с различными типами имплантатов ТИ выглядят более благоприятно по сравнению с ПУИ. Наличие ПУИ в тканях подавляет местный противоопухолевый иммунитет, что в дальнейшем может повысить вероятность местного рецидивирования.

What does endemic COVID-19 mean for the future of rituximab?

What does endemic COVID-19 mean for the future of rituximab?

Cell-mediated immunity in patients with post-CoVID syndrome

Aim: to study the investigate of the cell-mediate immunity in post-COVID syndrome. Material and Methods: 278 patients with mild, moderate or severe Covid-19 in acute period with post-COVID syndrome were examined. All patients were questioned, and, if necessary, were examined by doctors of various specialties. The patients were divided into 2 groups depending on the severity of the course of the disease in the acute period and the duration of manifestations of post-COVID symptoms (up to 12 weeks or more). The state of cell-mediated immunity was assessed using the reaction of blast transformation of peripheral blood lymphocytes (morphological method for evaluating the reaction) in response to PHA. The activity of cells synthesizing cyclooxygenase was also determined. The control group included 200 practically healthy people of the same sex and age, who were not vaccinated and did not have a coronavirus infection. Results: a decrease in the proliferative activity of lymphocytes in response to PHA was found in patients who underwent Covid-19, both in mild (51,4±1.1%, p&lt;0.01) and severe (49,3± 1,2% p&lt;0,001), more pronounced in the latter in the first three months after the acute period of the disease (p&lt;0,001). In all groups, there is an increase in the activity of cells synthesizing cyclooxygenase, which causes inflammation, which is more pronounced in patients who have had a severe form of Covid-19. Conclusion: The proliferative activity of peripheral blood lymphocytes in people who have had a coronavirus infection is reduced, both in the period up to 12 weeks and beyond; this is especially pronounced in patients who have had severe forms of Covid-19. In all groups, an increase in the activity of cells synthesizing cyclooxygenase, which plays a role in the development of inflammation, and possibly determines the progression of the course, was noted.

Study of the Serum Immunoglobulin and Cell-Mediated Immunity in Patients with Congenital Severe Hemophilia.

It has been shown that a close relationship exists between the immune system and coagulation cascade. Hemophilia A is an X-linked, recessive bleeding disorder caused by deficiency of functional plasma clotting factor VIII that is classically treated with factor VIII replacement therapy. Despite this, some patients produce inhibitors or antibodies against epitopes of infused factor VIII, indicating the activation of the adaptive immune system. The aim of this study was to evaluate the change in the T cell frequency and serum immunoglobulin level in patients with congenital hemophilia A, especially those who produce inhibitors against factor VIII. This is a cross-sectional, case-control study on congenital hemophilia A patients with severe factor VIII deficiency. Twenty-eight hemophilia A male patients were randomly selected along with twenty age-matched healthy males, as the control group. Serum immunoglobulin concentration was measured by nephelometry (for IgG, IgA and IgM) and enzyme-linked immunosorbent assay (ELISA) (for IgE) and the frequency of CD4+ and CD8+ T cells were calculated using a flow cytometry method. Serum IgG was significantly higher in hemophilic patients compared to controls (14.35 ± 3.60, vs. 12.4 ± 1.72, p = 0.014). Among IgG subtypes, the IgG1 antibody was significantly higher in hemophilia patients than control group (p < 0.001). The frequency of CD4+ as well as CD8+ T cells did not significantly differ between patients and control group (p > 0.05). There was no significant difference between patients with and without inhibitors re-garding serum immunoglobulin level, different IgG subtypes, the frequency of CD4+ and CD8+ T cells as well as CD4/CD8 ratio (p > 0.05). Patients with hemophilia A have high levels of serum immunoglobulin especially IgG1. Therefore, further larger studies along with close observation and evaluation of the presence of serum inhibitor is recommended every 3 months.

CELL MEDIATED IMMUNITY IN PATIENTS WITH STAGE II–IV COLORECTAL CANCER WITH OR WITHOUT CIRCULATING TUMOR CELLS

Nowadays, circulating tumor cells (CTCs) are considered to be one of the most important mechanisms of tumor dissemination. Detection of CTCs in patients` blood is estimated as a prognostic factor for various tumors including colorectal cancer (CRC). However, CTCs may also be a source of tumor antigens capable of inducing both immune response and tolerance and participating in «immmunoediting». The aim of the study was to assess the parameters of cell-mediated immunity in patients with stage IIIV CRC with respect to the presence or absence of CTCs. Materials and Methods . We studied the parameters of cell-mediated immunity in 60 patients with stage IIIV CRC with respect to the presence or absence of CTCs. Before treatment, we evaluated the CTC levels in patients’ blood using CellSearch System™ and lymphocyte subsets: Т-В-NК-cells, T-reg, CD4+ and CD8+ expressing markers of activation (CD69+, СD38+, CD25+, HLA-DR+ СD95+); naïve and memory T-lymphocytes (CD45RA-/CD45RO+); NК-cells expressing CD335, perforin and granzyme B using flow cytometry (FACSCantoII, BD). Results . A difference in the immunologic parameters between patients with CTCs and without CTCs depending on the stage of CRC was found. In СTС-positive patients with locally-advanced CRC, increase in the parameters of innate immunity (CD335+ NK-cells, neutrophils` respiratory burst) and activated Th (CD38+, CD25+, HLA-DR+) was found, while in СTС-positive patients with generalized CRC, suppression of cytotoxic lymphocytes of both innate (CD56/16+) and adaptive (CD8+CD25+) immunity was observed, which is, apparently, an unfavorable prognostic factor. Conclusion . The presence of CTC in CRC patients is accompanied by some immunologic changes rather stimulating Thlink and innate immunity factors in II-III stages and doubtlessly suppressive in patients with IV stage.

Suppressed T cell-mediated immunity in patients with COVID-19: A clinical retrospective study in Wuhan, China

ImportanceAn ongoing outbreak of COVID-19 has exhibited significant threats around the world. We found a significant decrease of T lymphocyte subsets and an increase of inflammatory cytokines of hospitalized patients with COVID-19 in clinical practice. MethodsWe conducted a retrospective, single-center observational study of in-hospital adult patients with confirmed COVID-19 in Hubei Provincial Hospital of traditional Chinese and Western medicine (Wuhan, China) by Mar 1, 2020. Demographic, clinical, laboratory information, especially T lymphocyte subsets and inflammatory cytokines were reported. For patients who died or discharge from hospital, the associations of T lymphocyte subsets on admission were evaluated by univariate logistic regression with odds ratios (ORs) and 95% confidence intervals (CIs), warning values to predict in-hospital death were assessed by Receiver Operator Characteristic (ROC) curves. ResultsA total of 187 patients were enrolled in our study from Dec 26, 2019 to Mar 1, 2020, of whom 145 were survivors (discharge = 117) or non-survivors (in-hospital death ==28). All patients exhibited a significant drop of T lymphocyte subsets counts with remarkably increasing concentrations of SAA, CRP, IL-6, and IL-10 compared to normal values. The median concentrations of SAA and CRP in critically-ill patients were nearly 4- and 10-fold than those of mild-ill patients, respectively. As the severity of COVID-19 getting worse, the counts of T lymphocyte drop lower.28 patients died in hospital, the median lymphocyte, CD3+ T-cell, CD4+ T-cell, CD8+ T-cell and B-cell were significantly lower than other patients. Lower counts (/uL) of T lymphocyte subsets lymphocyte (<500), CD3+T-cell (<200), CD4+ T-cell (<100), CD8+ T-cell (<100) and B-cell (<50) were associated with higher risks of in-hospital death of CIVID-19. The warning values to predict in-hospital death of lymphocyte, CD3+ T-cell, CD4+ T-cell, CD8+ T-cell, and B-cell were 559, 235, 104, 85 and 82, respectively. ConclusionWe find a significant decrease of T lymphocyte subset is positively correlated with in-hospital death and severity of illness. The decreased levels of T lymphocyte subsets reported in our study were similar with SARS but not common among other virus infection, which may be possible biomarkers for early diagnosis of COVID-19. Our findings may shed light on early warning of high risks of mortality and help early intervention and treatment of COVID-19.

Suppressed T Cell-Mediated Immunity in Patients with COVID-19: A Clinical Retrospective Study in Wuhan, China

Importance: An ongoing outbreak of COVID-19 has exhibited significant threats around the world. We found a significant decrease of T lymphocyte subsets and an increase of inflammatory cytokines of hospitalized patients with COVID-19 in clinical practice. Methods: We conducted a retrospective, single-center observational study of in-hospital adult patients with confirmed COVID-19 in Hubei Provincial Hospital of traditional Chinese and Western medicine (Wuhan, China) by Mar 1, 2020. Demographic, clinical, laboratory information, especially T lymphocyte subsets and inflammatory cytokines were reported. For patients who died or discharge from hospital, the associations of T lymphocyte subsets on admission were evaluated by univariate logistic regression with odds ratios (ORs) and 95% confidence intervals (CIs), warning values to predict in-hospital death were assessed by Receiver Operator Characteristic (ROC) curves. Results: A total of 187 patients were enrolled in our study from Dec 26, 2019 to Mar 1, 2020, of whom 145 were survivors (discharge= 117) or non-survivors (in-hospital death=28). All patients exhibited a significant drop of T lymphocyte subsets counts with remarkably increasing concentrations of SAA, CRP, IL-6, and IL-10 compared to normal values. The median concentrations of SAA and CRP in critically-ill patients were nearly 4- and 10-fold than those of mild-ill patients, respectively. As the severity of COVID-19 getting worse, the counts of T lymphocyte drop lower.28 patients died in hospital, the median lymphocyte, CD3+ T-cell, CD4+ T-cell, CD8+ T-cell and B-cell were significantly lower than other patients. Lower counts (/uL) of T lymphocyte subsets lymphocyte (<500), CD3+T-cell (<200), CD4+ T-cell (<100), CD8+ T-cell (<100) and B-cell (<50) were associated with higher risks of in-hospital death of CIVID-19. The warning values to predict in-hospital death of lymphocyte, CD3+ T-cell, CD4+ T-cell, CD8+ T-cell, and B-cell were 559, 235, 104, 85 and 82, respectively. Conclusion: We find a significant decrease of T lymphocyte subset is positively correlated with in-hospital death and severity of illness. The decreased levels of T lymphocyte subsets reported in our study were similar with SARS but not common among other virus infection, which may be possible biomarkers for early diagnosis of COVID-19. Our findings may shed light on early warning of high risks of mortality and help early intervention and treatment of COVID-19. Funding Statement: National science and technology emergency project-Clinical study on prevention and treatment of Corona Virus Disease 2019 by integrated traditional Chinese and western medicine (2020YFC0841600). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was reviewed and approved by the medical Ethical Committee of Hubei Provincial Hospital of traditional Chinese and Western medicine (NO.2020013). Written informed consent was obtained from every enrolled patient.

Hemodynamic Markers of Predominant Right Ventricular Dysfunction are Associated with Paradoxical Decreased Cell-Mediated Immunity in Patients with Advanced Heart Failure

Right ventricular dysfunction and decrease cellular immunity have been associated with worse prognosis in patients with advanced heart failure. Our objective was to evaluate if there was a relationship between hemodynamic parameters of right ventricular dysfunction and cell mediated immunity .

CELL-MEDIATED IMMUNITY IN PATIENTS WITH POSTTRAUMATIC LONG BONE OSTEOMYELITIS IN THE COURSE OF MANAGEMENT WITH THE ILIZAROV METHOD

Cell-mediated immunity parameters were studied in 26 patients (13 males, 13 females) aged 46 years (range: 39-51 years) with fistular type of chronic posttraumatic osteomyelitis of the humerus during the course of surgical treatment with the Ilizarov monofocal transosseous osteosynthesis. The study time-points were pre-surgery period and the following treatment stages: days 3, 7, 21 after osteosynthesis and day 1 after removal of the device. An obligatory criterion of inclusion was absence of postoperative complications and infection recurrence at least a year after removal of the apparatus. Control group were 30 healthy volunteers in the similar age (15 males, 15 females). Carriers of HCV, HIV, HBsAg and persons with concomitant somatic pathology that could affect the results of immunological study were not included. The study of subpopulation composition of the peripheral blood lymphocytes was carried out using laser flow cytometry. The parameters of cell-mediated immunity in patients with a fistular type of chronic posttraumatic osteomyelitis of the humerus were characterized by mild lymphopenia, increase in the number of cells of early and late activation of T lymphocytes (CD3 + CD25 + , CD3 + HLA-DR + ). Physiological response of the immune system to debridement of the purulent foci and transosseous osteosynthesis was normalization of the number of activated T-lymphocytes at the final stage of surgical treatment. In general, the dynamic changes of immunological indices were in favor of persistent arrest of the infection process and were confirmed by clinical observations.

Immune Status &#39;in Children with Beta Thalassemia&#39; in Correlation &#39;with Iron Overload&#39;: Single Center Egyptian Study.

'Beta thalassemia is inherited hemoglobin disorder resulting in chronic hemolytic anemia that requires lifelong transfusion therapy'. 'Repeated blood transfusions and RBCs hemolysis are the main causes of iron overload', which in addition to immune abnormalities, are common predisposing factors to infections in patients with thalassemia. The Aim of this Work: The aim of this work was to study immune status including T lymphocyte subsets and serum immunoglobulin levels 'in children with beta- thalassemia in correlation with iron overload'. The present 'study was conducted on 40 children with beta thalassemia major under follow up at Hematology Unit, Pediatric Department, Tanta University' 'including 24 males and 16 females with mean' age value of 9. 22 ± 3.9 years and 20 'healthy children of matched age and sex as a control group'. All children included in the study were subjected to; 'complete blood count, Hb electrophoresis, serum iron status', T cell subsets including CD3, CD4 and CD8 and serum immunoglobulin levels including IgM, IgA and IgG. 'Pallor and jaundice were the most common presenting' clinical manifestations. Infective episodes 'were significantly higher in patients' compared with controls. There were significantly lower Hb, MCV and MCH levels and significantly higher WBCs and platelets counts, reticulocytes and lymphocytes percentage in patients than controls and no significant differences in MCHC between patients and controls. Serum ferritin and iron were 'significantly higher but TIBC was significantly lower in' patients than controls. CD3, CD4 and IgM were significantly lower but CD8, IgG, and IgA 'were significantly higher in patients than controls' with negative correlation between CD3, CD4, IgM and ferritin and positive correlation between CD8, IgG, IgA and ferritin. Iron overload can affect humeral and cell mediated immunity in patients with beta thalassemia with reduction of IgM, CD3 and CD4 and elevation of CD8, IgG, and IgA. Regular follow up of patients with beta thalassemia for detection of iron overload as it affects humeral and cell mediated immunity.

Circulating IL-6 and neopterin concentrations link cell-mediated immunity and tumor stage in patients with gastro-intestinal adenocarcinoma: relevance to the pituitary-adrenal axis and pituitary-thyroid axis

Abstract Although cortisol is a powerful modulator of the immune system and inhibits production of pro-inflammatory cytokines, adrenocorticotropic hormone (ACTH) levels do not correspond to the chronically elevated concentrations of cortisol in cancer patients. Thyroid stimulating hormone (TSH) has been shown to have an effect on immunological functions. Actually it is not known whether cortisol, TSH and IL-6 have an effect on tumor progression via modulation of cell mediated immunity in patients with gastrointestinal carcinoma. Sixty-seven gastrointestinal cancer patients and 42 cancer-free subjects with cholelithiasis as the control group, were included in the study. Serum ACTH, cortisol, TSH, thyroid hormones, IL-6, IL-10 and neopterin levels were measured. Diagnosis and pathological staging were confirmed by surgical intervention. Cortisol levels were correlated with IL-6 in cancer patients. In addition to elevated neopterin values, linear regression analysis revealed that serum neopterin was associated more strongly with the increase of cortisol rather than IL-6 levels in advanced stage carcinoma. Furthermore, neopterin also correlated with IL-6, IL-10, cortisol and TSH levels in advanced carcinoma cases. These data indicated that cortisol, IL-6 and neopterin values of cancer patients were influenced by the tumor presence and progression.

Intraoperative intravenous lidocaine exerts a protective effect on cell-mediated immunity in patients undergoing radical hysterectomy.

Surgical procedures cause a decrease in lymphocyte proliferation rate, an increase in apoptosis and shifts the balance of T‑helper (Th)1/Th2 cells towards anti‑cell‑mediated immunity (CMI) Th2 dominance, which is relevant to the immunosuppressive effects of CMI, postoperative septic complications and the formation of tumor metastasis. Previous studies have revealed that lidocaine exhibits antibacterial actions; regulating inflammatory responses, reducing postoperative pain and affecting the duration spent in hospital. Thus, the present study hypothesized that lidocaine may exert a protective effect on the CMI of patients undergoing surgery for the removal of a primary tumor. A total of 30 adult female patients diagnosed with cervical cancer were recruited to the present study and were randomized into two groups. The lidocaine group received an intravenous bolus dose of 1.5 mg/kg lidocaine, followed by continuous infusion at 1.5 mg/kg/h until discharge from the operating room. The control group received the same volume of normal saline. A 10 ml sample of venous blood was drawn, and the lymphocytes were isolated using Ficoll‑paque 1 day prior to surgery, at discharge from the operating room and 48 h post‑surgery. The proliferation rate of the lymphocytes was assessed using a Cell Counting Kit‑8 assay and was found to be higher in the lidocaine group. The early apoptosis of lymphocytes was attenuated following lidocaine treatment at 48 h post‑surgery, as detected using flow cytometry with Annexin V‑fluorescein isothiocyanate/propidium iodide staining. The level of interferon (IFN)‑γ in the serum at 48 h was significantly decreased following surgery in the control group, compared with the pre‑surgical values (3.782 ± 0.282, vs. 4.089 ± 0.339 pg/ml, respectively) and the ratio of IFN‑γ to interleukin‑4 was well preserved in the lidocaine group. In conclusion, the present study demonstrated that the intraoperative systemic administration of lidocaine exerted a protective effect on CMI in patients with cervical cancer undergoing radical hysterectomy. This may be beneficial in reducing the occurrence of postoperative septic complications and tumor metastasis formation.

Varicella-zoster virus-specific cell-mediated immunity in Ramsay Hunt syndrome.

The etiology of Ramsay Hunt syndrome (Hunt syndrome) is reactivation of latent varicella-zoster virus (VZV) in the geniculate ganglion of the facial nerve, leading to neuritis. Although the mechanism of the VZV reactivation is unclear, one possibility is that the reactivation involves a low level of VZV-specific cell-mediated immunity (CMI). The aim of this study was to clarify the characteristics of the VZV-specific CMI in Hunt syndrome compared to that in Bell's palsy, and to obtain clues to its role in the development of Hunt syndrome. Prospective study. We determined the median spot numbers and examined VZV-specific CMI in patients with Hunt syndrome and with Bell's palsy using interferon-γ enzyme-linked immunospot (ELISPOT) assays. We analyzed the relationship between the value of VZV-specific CMI and days from disease onset. The median spot number in Hunt syndrome (87.3 spot-forming cells [SFCs]/4 × 10(5) peripheral blood mononuclear cells [PBMCs]) was higher than that in Bell's palsy (62.3 SFCs/4 × 10(5) PBMCs). Hunt syndrome showed a strong relationship between the ELISPOT count and days from onset (r = 0.65). Within the first 5 days from onset, no ELISPOT counts higher than 80 SFCs/4 × 10(5) PBMCs were observed. On the other hand, no correlation was observed between the ELISPOT count and days from onset in patients with Bell's palsy (r = -0.19). These results suggest that VZV-specific CMI in Hunt syndrome is low at disease onset and increases rapidly thereafter. Consequently, reduced VZV-specific CMI may play an important role in the reactivation of VZV in the facial nerve, leading to Hunt syndrome.

Good syndrome and polymyositis

Good syndrome (GS) was first described by Dr Robert Good in 1954 in an adult patient with thymoma and immunodeficiency. [1] Good R.A. Agammaglobulinaemia—a provocative experiment of nature. Bull Univ Minn. 1954; 26: 1-19 Google Scholar The immunodeficiency found in GS typically demonstrates low to absent B cells in the peripheral blood, hypogammaglobulinemia, and defects in cell-mediated immunity in patients 40 to 70 years of age. 2 Stiehm E.R. Ochs H.D. Winkelstein J.A. Immunologic Disorders in Infants & Children. WB Saunders, Philadelphia, PA2004 Google Scholar , 3 Kelleher P. Misbah S.A. Review: What is Good’s syndrome? immunological abnormalities in patients with thymoma. J Clin Pathol. 2003; 56: 12-16 Crossref PubMed Scopus (194) Google Scholar , 4 Joven M.H. Palalay M.P. Sonido C.Y. Case report and literature review on Good's syndrome, a form of acquired immunodeficiency associated with thymomas. Hawaii J Med Public Health. 2013; 72: 56-62 PubMed Google Scholar Infections associated with both B- and T-cell defects are common. [5] Tarr P.E. Sneller M.C. Mechanic L.J. et al. Infections in patients with immunodeficiency with thymoma (Good syndrome): report of 5 cases and review of the literature. Medicine. 2001; 80: 123-133 Crossref PubMed Scopus (197) Google Scholar

Schistosomiasis Does Not Affect the Outcome of HCV Infection in Genotype 4-Infected Patients

Although reports suggest that Schistosoma mansoni increases hepatitis C virus (HCV) morbidity and chronicity, its impact on HCV spontaneous resolution is not clear. HCV genotype, viral load, abdominal ultrasonographic findings, and HCV-specific cell-mediated immunity (CMI) were examined among 141 healthcare workers infected with HCV (68 workers with and 73 workers without S. mansoni). HCV genotype 4 was dominate, and viral loads were 2.62 ± 0.69 × 10(6) and 4.24 ± 1.4 × 10(6) IU/mL among patients with and without coinfection, respectively (P = 0.309); 23.5% with and 32.9% without coinfection had spontaneously resolved HCV infection (P = 0.297). Interferon-γ spot-forming cells/10(6) peripheral blood mononuclear cells among responding viremic patients with and without coinfection were 716 ± 194 and 587 ± 162, whereas among aviremic patients, it was 794 ± 272 and 365 ± 36 (P > 0.05), respectively. In conclusion, there was no statistical difference in HCV spontaneous resolution, viral load, liver pathology, or CMI in patients with or without S. mansoni coinfection, suggesting that it did not impact the outcome of HCV infection.

Effect of high dose inhaled corticosteroids on cell mediated immunity in patients with asthma

BackgroundCell mediated immunity is suppressed by systemic corticosteroids. Inhaled corticosteroids have been shown to affect parameters including bone metabolism, hypothalamus–pituitary adrenal axis, linear growth, and lead to the development of cataracts. However, it is unclear if high dose inhaled corticosteroid therapy affects cell mediated immunity. Study objectivesTo evaluate if asthma patients taking high dose inhaled corticosteroids chronically have reduced cell mediated immunity compared to asthma patients not taking inhaled corticosteroids. MethodsEighteen asthmatic subjects participated in this cross-sectional study. Cell mediated immunity was evaluated in nine patients who had been taking high dose inhaled corticosteroids for >6 months and nine patients not taking inhaled corticosteroids. Cell mediated immunity was evaluated by delayed type hypersensitivity (DTH) skin testing with intradermal placement of candida and tetanus antigens. ResultsThere was no significant difference in DTH skin test results between the high dose inhaled corticosteroid and no corticosteroid treated asthma group. ConclusionPatients with asthma taking high dose inhaled corticosteroids chronically (>6 months) did not have significantly greater impaired cell mediated immunity than patients not taking inhaled corticosteroids in this study.

Treatment with lenalidomide modulates T‐cell immunophenotype and cytokine production in patients with chronic lymphocytic leukemia

Lenalidomide, an immunomodulatory agent, has activity in lymphoproliferative disorders. The authors, therefore, evaluated its effects on T-cell immunophenotype and cytokine production in patients with chronic lymphocytic leukemia (CLL). To study the immunomodulatory effects of lenalidomide in CLL, the authors recruited 24 patients with untreated CLL enrolled in a phase 2 clinical trial of lenalidomide and obtained peripheral blood specimens for immunologic studies consisting of enumeration of T cells and assessing their ability to synthesize cytokines after activation through T-cell receptor (TCR). After 3 cycles of therapy, patients had a significant reduction in percentage (%) and absolute lymphocyte count (ALC) and an increase in percentage of T cells, percentage of activated CD8(+) T cells producing IFN-γ, and percentage of regulatory T (T(R) ) cells when compared with their respective levels before treatment. After 15 cycles of treatment, responder patients had significant reduction in percentage of lymphocytes and ALC, percentage of activated CD4(+) T cells producing IL-2, IFN-γ, or TNF-α, and percentage of T(R) cells when compared with their perspective levels after 3 cycles of treatment. Furthermore, the numbers of activated CD4(+) T cells producing IL-2, IFN-γ, or TNF-α, activated CD8(+) T cells producing IFN-γ, and T(R) cells normalized to the range of healthy subjects. Treatment with lenalidomide resulted in the normalization of functional T-cell subsets in responders, suggesting that lenalidomide may modulate cell-mediated immunity in patients with CLL.

Identification of Multiple HLA Class II Epitopes of Aspergillus Fumigatus by Generation of CD4+ T Cell Clones Recognizing the A. Fumigatus proteins Crf1 and Catalase1

AbstractAbstract 2332Invasive aspergillosis is a common and life-threatening complication in recipients of allogeneic stem cell transplantation. Patients are at risk in the neutropenic phase, but also after recovery of the neutrophil count there is an increased risk of developing invasive aspergillosis, probably caused by other defects in the innate immune system, or by impaired T cell mediated immunity after stem cell transplantation. In healthy individuals and in patients lymphoproliferative responses to crude Aspergillus extracts and recombinant antigens have been shown. Furthermore, patients after haploidentical stem cell transplantation were less susceptible to aspergillus infection when transferred with T cell lines generated against Aspergillus fumigatus. To facilitate the study of the role of T cell mediated immunity in aspergillus infection and develop new therapeutic strategies to prevent or treat invasive aspergillosis we aimed to identify T cell epitopes of Aspergillus fumigatus.Peripheral blood mononuclear cells (PBMC) of healthy individuals were stimulated with overlapping 15mer peptides of the Aspergillus fumigatus proteins Crf1 and Catalase1. Directly after stimulation no antigen specific T cells could be detected, however after stimulation with the complete peptide pool, IL-2 and IL-15 for 7 days and subsequent restimulation with peptide pulsed autologous PBMC an increase of activated T cells could be detected in half of the healthy donors, based on IFNγ production, CD154 (CD40 ligand) and CD137 expression. From 6 donors antigen specific CD4+ T cells were single cell sorted 4 hours after restimulation with the complete peptide pool using the IFNγ capture assay or by sorting the CD137+ CD4+ T cells 48 hours after restimulation with the complete peptide pool and cells were clonally expanded. The generated T cell clones were tested for Aspergillus peptide specificity against the complete peptide pool using ELISA to determine the IFNy and IL-4 production. Aspergillus peptide specific clones were further analyzed with subpools of the overlapping peptides, to identify the specific T cell epitope. These subpools are organized in a matrix to enable us to identify the recognized epitope directly from this analysis. Subsequently, the T cell clones were stimulated with the single recognized peptides to confirm the identified epitopes. Five different T cell epitopes of Crf1 were identified: one epitope at position 161–171, which was previously described, and four novel epitopes. For the Catalase1 protein we identified 7 different epitopes, which have not been described before. By using HLA-blocking monoclonal antibodies and an HLA-typed EBV-LCL panel we determined the HLA-restriction of the different T cell epitopes. Two Crf1 epitopes and three Catalase1 epitopes were HLA-DR restricted, and one of the Crf1 epitopes was presented by HLA-DP. The HLA-restriction of the other 6 identified epitopes has not yet been characterized. The T cell clones showed 3 different patterns of cytokine production. Some clones only produced IFNγ, some clones only IL-4 and others produced both IFNγ and IL-4.Twelve T cell epitopes in two different proteins of Aspergillus fumigatus, presented by various HLA class II molecules, were identified. The generated T cell clones showed a variable pattern of cytokine production. To evaluate whether all these epitopes are relevant for the immune response against aspergillosis, the specificity against Aspergillus fumigatus will be tested by incubating T cells and dendritic cells with inactivated fungus. If Aspergillus-specificity is demonstrated, these epitopes can be used to study T cell mediated immunity in patients with aspergillosis and be a first step towards new therapeutic options for invasive aspergillosis. Disclosures:No relevant conflicts of interest to declare.