scholarly journals THU0031 ABATACEPT ALTERS THE FREQUENCY OF IMMUNOREGULATORY AND EFFECTOR T CELL SUBPOPULATIONS IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 229.2-229
Author(s):  
B. Dreo ◽  
B. Prietl ◽  
S. Kofler ◽  
H. Sourij ◽  
A. Lackner ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
T Cell ◽  
Autoimmune Diseases ◽  
T Cell Subsets ◽  
Cell Phenotype ◽  
Effector T Cell ◽  
Cell Subpopulations ◽  
T Cell Subpopulations ◽  
The Impact

Background:Under physiological conditions, T regulatory cells (Tregs) are responsible for the downregulation of the immune response. In autoimmune diseases, such as rheumatoid arthritis (RA), auto-inflammation is driven by an imbalance of activation and downregulation of immunological pathways. Thus, treatment plans for autoimmune diseases often involve the enhancement of immunoregulatory pathways by administering inhibitors of costimulation, i.e. CTLA-4-Ig (abatacept, ABA). ABA binds specifically to CD80 and CD86 on antigen presenting cells (APC). Consequently, T cell activation via the CD28 receptor is blocked. Previous studies have demonstrated surprising effects of abatacept on Tregs, specifically decreased frequency of these cells but enhancement in their function1. Whether these alterations can only be found in patients with ABA treatment, or whether they are also present in patients receiving other anti-inflammatory drugs is currently unknown.Objectives:The aim of our research was to delineate the impact of ABA on the different subsets of effector and regulatory T cells in RA and compare these findings with patients receiving tocilizumab (TCZ) or rituximab (RTX).Methods:Peripheral blood samples from 56 RA patients (median ± SE; age: 60.5 ± 1.3 years, female ratio: 0.7, disease duration: 17.9 ± 2.1 years; respectively) were drawn over a sampling period of 2 years. Freshly isolated PBMCs of RA patients were stained with fluorochrome-labelled antibodies and T cell subsets were identified by flow cytometric means. CD3+CD4+T cells were further classified using different T cell markers (CD25, CD127, CD39, CD95). All cytometric measurements were performed using a standardized BD LSR-Fortessa platform. RA patients were compared according to their treatment with ABA, TCZ or RTX.Results:Eighteen out of 56 RA patients (32%) received ABA, 25 patients (45%) received TCZ and 13 patients (23%) were under CD20+ cell depletion therapy with RTX. RA patients receiving ABA displayed a significant decrease in CD3+CD4+CD25+CD127dimTregs (3.7% ± 0.4) compared to patients with TCZ (5.4% ± 0.4, p = 0.041) and patients under RTX treatment (7.52% ± 0.93, p = 0.026). CD39+Tregs were significantly higher in RA patients treated with TCZ (49.5% + 3.2, p = 0.000) or RTX (50.5% ± 5.3, p = 0.026) compared to patients receiving ABA (24.5% ± 3.1). In addition, the frequency of CD95+Tregs was significantly reduced in ABA patients compared to RTX patients (59.6% ± 3.1 vs.76.7% ± 3.6, p = 0.014; respectively). Interestingly, T cells displaying an effector T cell phenotype (CD3+CD4+CD25+/-CD127+) were increased in ABA treated patients compared to RTX treated patients (59.6% ± 3.1 and 76.7% ± 3.6, p = 0.002). Since none of our patients were a non-responder or had high disease activity, we could not analyse whether these changes are associated with treatment outcome.Conclusion:Our data demonstrate that blockage of T cell stimulation via ABA leads to characteristic alterations in different regulatory and effector T cells not seen in patients treated with TCZ or RTX. Further studies must clarify whether the analysis of regulatory and effector T cell subpopulations before treatment initiation can be used as biomarker for treatment response.References:[1]Álvarez-Quiroga C, Abud-Mendoza C, Doníz-Padilla L, et al. CTLA-4-Ig therapy diminishes the frequency but enhances the function of treg cells in patients with rheumatoid arthritis.J Clin Immunol. 2011;31(4):588-595.doi:10.1007/s10875-011-9527-5Acknowledgments:Work done in “CBmed” was funded by the Austrian Federal Government within the COMET K1 Centre Program, Land Steiermark and Land Wien.Disclosure of Interests:None declared

scholarly journals Human papillomavirus oncoproteins induce a reorganization of epithelial-associated γδ T cells promoting tumor formation

2017 ◽  
Vol 114 (43) ◽  
pp. E9056-E9065 ◽  
Author(s):  
Dorien Van hede ◽  
Barbara Polese ◽  
Chantal Humblet ◽  
Anneke Wilharm ◽  
Virginie Renoux ◽  
...  
Keyword(s):  
T Cells ◽  
Human Papillomavirus ◽  
T Cell ◽  
Γδ T Cells ◽  
Tumor Formation ◽  
T Cell Subsets ◽  
Γδ T Cell ◽  
Cell Subpopulations ◽  
T Cell Subpopulations ◽  
The Impact

It has been shown that γδ T cells protect against the formation of squamous cell carcinoma (SCC) in several models. However, the role of γδ T cells in human papillomavirus (HPV)-associated uterine cervical SCC, the third-leading cause of death by cancer in women, is unknown. Here, we investigated the impact of γδ T cells in a transgenic mouse model of carcinogenesis induced by HPV16 oncoproteins. Surprisingly, γδ T cells promoted the development of HPV16 oncoprotein-induced lesions. HPV16 oncoproteins induced a decrease in epidermal Skint1 expression and the associated antitumor Vγ5+ γδ T cells, which were replaced by γδ T-cell subsets (mainly Vγ6+ γδlowCCR2+CCR6−) actively producing IL-17A. Consistent with a proangiogenic role, γδ T cells promoted the formation of blood vessels in the dermis underlying the HPV-induced lesions. In human cervical biopsies, IL-17A+ γδ T cells could only be observed at the cancer stage (SCC), where HPV oncoproteins are highly expressed, supporting the clinical relevance of our observations in mice. Overall, our results suggest that HPV16 oncoproteins induce a reorganization of the local epithelial-associated γδ T-cell subpopulations, thereby promoting angiogenesis and cancer development.

scholarly journals T-Cell Subsets in Rheumatoid Arthritis Patients on Long-Term Anti-TNF or IL-6 Receptor Blocker Therapy

2017 ◽  
Vol 2017 ◽  
pp. 1-19 ◽  
Author(s):  
Sonja Dulic ◽  
Zsófia Vásárhelyi ◽  
Florentina Sava ◽  
László Berta ◽  
Balázs Szalay ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
T Cell ◽  
T Cell Subsets ◽  
Cell Phenotype ◽  
Healthy Controls ◽  
Biological Therapies ◽  
Cd8 Cells ◽  
The Impact

Data on the impact of biological therapies on the T-cell phenotype in rheumatoid arthritis are limited. Here, we prospectively measured the percentages of 15 circulating T-cell subtypes using flow cytometry. We obtained transversal and longitudinal data in 30 anti-TNF responders, 19 secondary anti-TNF nonresponders, and 43 IL-6R antagonist responders, before, 8 weeks and at least 6 months after biological therapy. Untreated RA patients and healthy controls were also included. The important findings are the following: (1) the proportion of regulatory T-cells (Tregs) which are decreased in untreated RA patients becomes normal in all long-term-treated groups; (2) in anti-TNF responders as well as in nonresponders, the frequencies of naïve CD4+ and CD8+ cells are lower, whereas those of proinflammatory Th1, Th2, and Th17 cells and HLA-DR+-activated cells are higher than those in untreated RA or healthy controls; (3) in IL-6R responders, Th1 proportion is decreased, while that of Th2 and Th17 is increased as compared to that in anti-TNF-treated patients and controls; (4) pending confirmation, a CD4CD69 ratio < 2.43 at baseline, could be useful to predict a good therapeutic response to anti-TNF therapy. This study provides comprehensive information regarding the long-term impacts of those biological therapies on the ecotaxis of T-cells in RA. The ClinicalTrials.gov registration number of our study is NCT03266822.

scholarly journals Impact of Vaccination on Distribution of T Cell Subsets in Antiretroviral-Treated HIV-Infected Children

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Premrutai Thitilertdecha ◽  
Ladawan Khowawisetsut ◽  
Palanee Ammaranond ◽  
Poonsin Poungpairoj ◽  
Varangkana Tantithavorn ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Viral Replication ◽  
Cd4 Count ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Influenza A H1n1 ◽  
Cell Subpopulations ◽  
T Cell Subpopulations ◽  
The Impact

Antiretroviral therapy (ART) is generally prescribed to patients with human immunodeficiency virus (HIV) infection with vaccination introduced to prevent disease complications. However, little is known about the influence of immunization on T cell subsets’ distribution during the course of infection. This study aims to identify the impact of viral replication and immunization on naïve, effector, effector memory, and central memory T cell subpopulations in ART-treated HIV-infected children. Fifty patients were recruited and injected intramuscularly with influenza A (H1N1) 2009 vaccine on the day of enrollment (day 0) and day 28. Blood samples were collected for pre- and postvaccination on days 0 and 56 for analyzing T cell phenotypes by flow cytometry. Phenotypes of all T cell subsets remained the same after vaccination, except for a reduction in effector CD8+ T cells. Moreover, T cell subsets from patients with controllable viral load showed similar patterns to those with virological failure. Absolute CD4 count was also found to have a positive relationship with naïve CD4+ and CD8+ T cells. In conclusion, vaccination and viral replication have a little effect on the distribution of T cell subpopulations. The CD4 count can be used for prediction of naïve T cell level in HIV-infected patients responding to ART.

Probing the Impact of AMD3100/GCSF Mobilization on the Peripheral Blood T Cell Content Using a Rhesus Macaque Model: Increased Proportions of FoxP3+/CD4+ T Cells Occur After Mobilization and Leukapheresis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 350-350
Author(s):  
Leslie Kean ◽  
Sharon Sen ◽  
Mark E Metzger ◽  
Aylin Bonifacino ◽  
Karnail Singh ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Cell Populations ◽  
Macaque Model ◽  
Cd34 Cells ◽  
Cell Subpopulations ◽  
T Cell Subpopulations ◽  
The Impact

Abstract Abstract 350 Introduction: Leukapheresis is a widely utilized modality for collecting hematopoietic stem cells (HSCs). While collection of CD34+ cells with stem-cell activity is the primary goal of most mobilization and leukapheresis procedures, these cells only represent ∼1% of most leukapheresis products. The profile of the non-CD34+ cells is likely influenced by the choice of mobilization strategy, and has the potential to profoundly impact the post-transplant immune milieu of the transplant recipient. Two of the most critical of the CD34-negative cell populations that are collected during leukapheresis include effector and regulatory T cells. Thus, in evaluating mobilization regimens, the impact on these regimens on the mobilization of each of these T cell populations into the peripheral blood should be rigorously evaluated. Methods: We used a rhesus macaque model to determine the impact that mobilization with AMD3100 (a.k.a., Plerixafor or Mozobil®)+ G-CSF (“A+G”) had on peripheral blood CD4+ and CD8+ effector T cell populations as well as on FoxP3+/CD4+ T cells. Three rhesus macaques were mobilized with 10ug/kg SQ of G-CSF for five consecutive days prior to leukapheresis. AMD3100 was administered at 1mg/kg SQ in combination with the last dose of G-CSF two hours prior to leukapheresis. Leukapheresis procedures were performed for two hours using a modified CS3000 Plus cell separator. A peripheral blood sample was taken before cytokine therapy, just prior to leukapheresis following mobilization, one hour during leukapheresis, and at the end of the procedure. These samples were analyzed by multicolor flow cytometry using a BD LSRII flow cytometer. Results: Bulk, effector, and regulatory T cell subpopulations were analyzed flow cytometrically. The proportion of total CD3+ T cells remained stable during mobilization and apheresis: Thus, CD3+ T cells represented 77% of peripheral blood lymphocytes prior to mobilization, and 69% post-apheresis). The balance of CD4+ to CD8+ T cells was also relatively stable. Thus, for one of the three animals tested, the CD4+ and CD8+ proportions remained unchanged after apheresis. For two animals, the average CD4+ % decreased from 67% prior to mobilization to 52% post-apheresis. In these two animals, there was a reciprocal increase in the % of CD3+ T cells that were CD8+ (28% pre-G+A to 40% post-apheresis). The CD28+/CD95- naïve (Tn), CD28+/CD95+ central memory (Tcm) and CD28-/CD95+ effector memory (Tem) subpopulation balance of CD4+ and CD8+ T cells was also determined, by comparing the relative percentages of each subpopulation post-apheresis with their relative percentages prior to mobilization. Compared to their pre-G+A percentages, the post-apheresis CD4+ percentages of Tn, Tcm and Tem were 92%, 93% and 160%, respectively. Thus, the relative proportions of Tn and Tcm CD4+ cells decreased post-apheresis, while the relative proportion of CD4+ Tem increased compared to cytokine administration. For CD8+ T cell subpopulations, the post-apheresis proportions of Tn, Tcm, and Tem compared to their pre-G-CSF proportions were 99%, 70% and 130%, respectively–thus demonstrating the same direction of change as observed for CD4+ T cells. The most striking change in T cell subpopulations occurred in the CD4+/FoxP3+ compartment. The proportion of CD4+ T cells expressing FoxP3 increased by an average of 600% when post-apheresis samples were compared to pre-mobilization samples (FoxP3+ cells were 9.6% of CD4+ T cells post-apheresis versus 1.5% pre-GCSF). An average of 32% of these FoxP3+ CD4+ T cells expressed high levels of CXCR4. CXCR4 expression has been previously documented on human FoxP3+ T cells (Zou et al., Cancer Res, 2004), but this is the first observation of high level expression of CXCR4 on macaque FoxP3+ CD4 T cells, or of their ability to be efficiently mobilized with AMD3100. Discussion: These results suggest that treatment with AMD3100 and G-CSF may mobilize T cell subsets into the peripheral blood that could have beneficial effects during allo-transplantation. The combination of an increase in Tem cells, which have been observed to have decreased ability to cause GvHD (Zheng et al., Blood 2008), along with FoxP3+/CD4+ T cells, which may have regulatory functions, suggests that A+G mobilization could produce an apheresis product with a beneficial CD34-negative cell profile for allogeneic transplantation. Disclosures: No relevant conflicts of interest to declare.

Impact of CMV and age on T cell subsets defined by CD161, CD300a, and/or CD57 expression in healthy Andalusians

2021 ◽  
Author(s):  
Martina Formentini ◽  
Ana Navas ◽  
Fakhri Hassouneh ◽  
Nelson Lopez-Sejas ◽  
Corona Alonso ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Subsets ◽  
Molecular Signature ◽  
Cmv Infection ◽  
Age Related ◽  
Increased Risk ◽  
Cell Subpopulations ◽  
New Biomarkers ◽  
T Cell Subpopulations

Abstract Immunosenescence affects innate and adaptive immunity impairing the response to pathogens and vaccines. Chronic infection with cytomegalovirus (CMV) has been shown to drive ‘early immunosenescence’ and can considerably impact both the function and phenotype of immune cells, especially T cells. We have previously shown that the expression of CD57, CD300a, and CD161 was differentially affected by age and chronic CMV infection, indicating that these markers are a hallmark of CMV infection and T cell ageing. The aim of this present study was to clarify whether these three markers define distinct T cell subpopulations with a specific functional and molecular signature. Specifically, we analyzed the effect of age and chronic CMV infection on the functionality of T cells according to CD161, CD300a, and CD57 expression. We found that these markers defined different T cell subsets, both at the phenotypic and functional levels. CD57 was the best biomarker for CD4+ T cell cytotoxicity and was a hallmark of CMV infection. CD300a+ T cells were heterogeneous and included different cell subsets. The population of CD161+ T cells dramatically decreased with age, independently of CMV infection, and represented a sign of age-associated immune system alterations. The latter could contribute to an increased risk of autoimmune disease and infection in older adults. Our results underline the importance of better understanding the factors involved in the immunosenescence process to be able to uncover new biomarkers and open new avenues for the investigation and development of novel age-related disease therapies.

scholarly journals The detailed distribution of T cell subpopulations in immune-stable renal allograft recipients: a single center study

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6417 ◽  
Author(s):  
Quan Zhuang ◽  
Bo Peng ◽  
Wei Wei ◽  
Hang Gong ◽  
Meng Yu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Renal Allograft ◽  
T Cell Subsets ◽  
Post Transplantation ◽  
Immune State ◽  
Hla Dr ◽  
Cell Subpopulations ◽  
T Cell Subpopulations ◽  
Diverse Groups

Background Most renal allograft recipients reach a stable immune state (neither rejection nor infection) after transplantation. However, the detailed distribution of overall T lymphocyte subsets in the peripheral blood of these immune-stable renal transplant recipients remains unclear. We aim to identify differences between this stable immune state and a healthy immune state. Methods In total, 103 recipients underwent renal transplantation from 2012 to 2016 and received regular follow-up in our clinic. A total of 88 of these 103 recipients were enrolled in our study according to the inclusion and exclusion criteria. A total of 47 patients were 1 year post-transplantation, and 41 were 5 years post-transplantation. In addition, 41 healthy volunteers were recruited from our physical examination clinic. Detailed T cell subpopulations from the peripheral blood were assessed via flow cytometry. The parental frequency of each subset was calculated and compared among the diverse groups. Results The demographics and baseline characteristics of every group were analyzed. The frequency of total T cells (CD3+) was decreased in the renal allograft recipients. No difference in the variation of the CD4+, CD8+, and activated (HLA-DR+) T cell subsets was noted among the diverse groups. Regarding T cell receptor (TCR) markers, significant reductions were found in the proportion of γδ T cells and their Vδ2 subset in the renal allograft recipients. The proportions of both CD4+ and CD8+ programmed cell death protein (PD) 1+ T cell subsets were increased in the renal allograft recipients. The CD27+CD28+ T cell proportions in both the CD4+ and CD8+ populations were significantly decreased in the allograft recipients, but the opposite results were found for both CD4+ and CD8+ CD27-CD28- T cells. An increased percentage of CD4+ effector memory T cells and a declined fraction of CD8+ central memory T cells were found in the renal allograft recipients. Conclusion Limited differences in general T cell subsets (CD4+, CD8+, and HLA-DR+) were noted. However, obvious differences between renal allograft recipients and healthy volunteers were identified with TCR, PD1, costimulatory molecules, and memory T cell markers.

Bone Marrow T Cell Subpopulations in Patients with Newly Diagnosed B-Cell Precursor Acute Lymphoblastic Leukemia (ALL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4278-4278
Author(s):  
Peter Brinkrolf ◽  
Silke Landmeier ◽  
Bianca Altvater ◽  
Sibylle Pscherer ◽  
Annegret Rosemann ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Γδ T Cells ◽  
Risk Groups ◽  
T Cell Subsets ◽  
Cell Precursor ◽  
Medium Risk ◽  
Pediatric All ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

Abstract Besides its role in hemato- and lymphopoiesis, bone marrow (BM) has emerged as a secondary lymphoid organ with important roles in both T cell priming and memory responses. Due to these properties, non-malignant T cells persisting within the BM of patients with acute leukemias may be involved in the immune response to leukemia and the control of minimal residual disease. Here, we investigated the phenotypic signature of residual T cells present at diagnosis in 25 pediatric patients (age 2–16 years) with B cell precursor ALL. Patients with high risk disease including Philadelphia chromosome-positive or MLL-rearranged leukemias were excluded from this analysis. Mononuclear cells were isolated from freshly aspirated BM by density gradient centrifugation and analyzed by six-color-flow cytometry using monoclonal antibodies directed towards various T-cell associated surface and intracellular markers, including CD3/CD56/TCRαβ/TCRγδ/CD86/HLA-DR (Panel 1); CD3/CD4/CD8/CCR7/CD45RA/ CD45RO (Panel 2); CD4/FoxP3/CD25/CD45RA/CD45RO/CCR7 (Panel 3). For each sample, ≥15,000 CD3+ cells (Panel 1, 2) or ≥8,000 CD4+ cells (Panel 3) were analyzed with FACS Canto and Diva Software. The Student’s t test was used to determine statistical significances between individual subgroups, and correlations were performed using the Pearson test. Consistent with published data on BM T cell subsets in healthy donors, the CD4+/CD8+ T cell ratio was 1.32±0.41. The predominant subset among CD8+ T cells (55.2±17.6%) had a naïve T cell phenotype (CD45RA+CCR7+), while 20.7±11.5% were effector memory T cells (TEM; CD45RA-CCR7-), and 7.1±6.2% were central memory T cells (TCM; CD45RA-CCR7+). No differences were found between TEL/AML1 positive or negative leukemias, or between patients stratified into standard (SR) vs. medium risk (MR) groups according to the criteria of the ALL-BFM 2000 study group. T cells bearing γδ T cell receptors have been attributed important roles in the primary immune defense against microbes and in immune control of cancer. We found that 6.9±3.0% (1.8 to 11.8%) of BM T cells were γδTCR+ (Vγ9Vδ2). A statistically significant (p <0.02) difference in the percentage of γδ T cells was found in patients stratified within risk groups MR and SR, respectively (7.0 vs. 4.5%). BM was further found to be a significant reservoir for regulatory T cells (Tregs). The presence of Tregs in the tumor microenvironment has been correlated with an unfavorable prognosis in many types of cancer, indicating a role in tumor immune escape. We found a proportion of 3.6±1.6% FoxP3+CD4+CD25high Tregs among BM CD4+ T cells from all ALL patients. Again, no significant differences were found according to TEL/AML1 status or risk stratification. Recent attention was drawn on the existence of both naïve and memory Treg subpopulations, differing by their expression of CD45RA and CCR7, and conflicting results were reported regarding the relative frequency of either subpopulation. We found a slight predominance of TEM Tregs (47.4±11.4%) above naïve (36.0±10.1%) and TCM Tregs (9.8±4.4%). In summary, while γδ T cells were found at significantly distinct numbers between patients stratified into standard and medium risk groups, no major phenotypic differences were found in residual BM αβ T cell subsets between individual subgroups in non-high-risk pediatric ALL. Future experiments will establish the functional role of the T cell subpopulations in immune control or escape in pediatric ALL.

scholarly journals T-Cell Receptor Vβ Repertoire CDR3 Length Diversity Differs within CD45RA and CD45RO T-Cell Subsets in Healthy and Human Immunodeficiency Virus-Infected Children

2000 ◽  
Vol 7 (6) ◽  
pp. 953-959 ◽  
Author(s):  
Zhong Chen Kou ◽  
Joshua S. Puhr ◽  
Mabel Rojas ◽  
Wayne T. McCormack ◽  
Maureen M. Goodenow ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Cell Receptor ◽  
T Cell Subsets ◽  
Cdr3 Length ◽  
Immunodeficiency Virus ◽  
Tcr Repertoire ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

ABSTRACT The T-cell receptor (TCR) CDR3 length heterogeneity is formed during recombination of individual Vβ gene families. We hypothesized that CDR3 length diversity could be used to assess the fundamental differences within the TCR repertoire of CD45RA and CD45RO T-cell subpopulations. By using PCR-based spectratyping, nested primers for all 24 human Vβ families were developed to amplify CDR3 lengths in immunomagnetically selected CD45RA and CD45RO subsets within both CD4+ and CD8+ T-cell populations. Umbilical cord blood mononuclear cells or peripheral blood mononuclear cells obtained from healthy newborns, infants, and children, as well as human immunodeficiency virus (HIV)-infected children, were analyzed. All T-cell subsets from newborn and healthy children demonstrated a Gaussian distribution of CDR3 lengths in separated T-cell subsets. In contrast, HIV-infected children had a high proportion of predominant CDR3 lengths within both CD45RA and CD45RO T-cell subpopulations, most commonly in CD8+ CD45RO T cells. Sharp differences in clonal dominance and size distributions were observed when cells were separated into CD45RA or CD45RO subpopulations. These differences were not apparent in unfractionated CD4+ or CD8+ T cells from HIV-infected subjects. Sequence analysis of predominant CDR3 lengths revealed oligoclonal expansion within individual Vβ families. Analysis of the CDR3 length diversity within CD45RA and CD45RO T cells provides a more accurate measure of disturbances in the TCR repertoire than analysis of unfractionated CD4 and CD8 T cells.

scholarly journals P0297CHANGES OF CD4CD28NULL AND CD8CD28NULL T CELLS IN CHRONIC KIDNEY DISEASE AND THE IMPACT OF DIFFERENT DIALYSIS MODALITIES

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Erasmia Sampani ◽  
MARIA STANGOU ◽  
Dimitra Vasileia Daikidou ◽  
Vasiliki Nikolaidou ◽  
Despoina Asouchidou ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
T Cells ◽  
T Cell ◽  
Kidney Disease ◽  
Cell Immunity ◽  
Clinical Consequences ◽  
Cell Subpopulations ◽  
And Gender ◽  
T Cell Subpopulations ◽  
The Impact

Abstract Background and Aims Chronic Kidney Disease (CKD) affects both the innate and adaptive immunity, although clinical consequences, and the effect of different renal replacement methods on those alterations remain unclear. The purpose of this prospective observational study was to investigate the alterations of T cell immunity in CKD patients, as well as the effect of different dialysis methods on T lymphocyte subtypes. Method T cell subpopulations namely CD3+CD4+, CD3+CD8+, CD4+CD28- and CD8CD28- cells, were isolated from whole blood samples using flow cytometry in 40 CKD patients at predialysis state (ESRD-T0). The immunological profile was repeated six months later after initiation of renal replacement therapy (hemodialysis (HD) or peritoneal dialysis (CAPD)). Fifteen age and gender matched healthy individuals served as controls. Results Both CD4+ and CD8+ T cells were significantly reduced in ERSD-T0 patients compared to controls, 604(105-3551) vs. 943(584-1867) μ/L, p=0.001, and 352(103-1561) vs. 422.4(263-1453) μ/L, p=0.05. The percentage of both CD4+CD28null and CD8+CD28null cells, 6.4(0.3-30) % vs. 2.7(0.1-7.8) %, p=0.04 and 58.2(12.8-85.4) % vs. 39(7.8-57.1) %, p=0.01 was increased in ERSD-T0 patients comparing to controls. Furthermore the percentage of CD4+CD28null cells correlated with CRP (r=0.4, p=0.04) and serum albumin levels (r=-0.5, p=0.007), while, significant differences were noticed between patients with and without cardiovascular disease, regarding both, CD4+CD28null and CD8+CD28null cells, 8.6(1-30) % vs. 2.1(0.1-19.8) %, p=0.04 and 62.5(12.8-85.4) vs. 45.5(5.7-73.7), p=0.02, respectively. Changes in the population of CD4+CD28null after 6 months on dialysis showed significant differences between HD and CAPD methods, 110.11(-27.1 to 311.4)% vs. -28.1(-100 to 30)%, respectively, p=0.003, as were in CD8+CD28null cells, 55.23(-29.06 to 197.93)% vs. -8.34(-54.99 to 66.72)%, respectively, p=0.05. Conclusion CKD seem to affect specific T cell subtypes, at a pre-dialysis stage, and levels correlate with chronic inflammatory markers and the presence of CVD. These disturbances are further enhanced in HD, while they are alleviated in CAPD.

scholarly journals T cell subsets defined by expression of Lyt-1,2,3 and Thy-1 antigens. Two-parameter immunofluorescence and cytotoxicity analysis with monoclonal antibodies modifies current views.

1980 ◽  
Vol 152 (2) ◽  
pp. 280-295 ◽  
Author(s):  
J A Ledbetter ◽  
R V Rouse ◽  
H S Micklem ◽  
L A Herzenberg
Keyword(s):  
T Cells ◽  
Monoclonal Antibodies ◽  
Lymph Node ◽  
T Cell ◽  
T Cell Subsets ◽  
Quantitative Expression ◽  
Cell Subpopulations ◽  
Spleen And Lymph Nodes ◽  
T Cell Subpopulations ◽  
T Cell Maturation

Using monoclonal antibodies and multiparameter fluorescence analyses, we show that the expression of Lyt-1, Lyt-2, and Lyt-3 on T cell subpopulations is more complex than was originally recognized by the cytotoxic depletion studies with conventional reagents that defined the Lyt-1+2+3+, Lyt-1+2-3-, and Lyt-1-2+3+ populations. We detect at least some Lyt-1 on all T (Thy-1-bearing) lymphocytes; however, in agreement with previous studies, we find that Lyt-2+3+ cells are more difficult to depelete with anti-Lyt-1 than Lyt-1+2-3- cells. Surprisingly, we found a small subpopulation of cells carrying relatively large amounts of Lyt-1 and no Thy-1 detectable by fluorescence-activated cell sorter analysis. We also detect cells with this phenotype histologically in B cell zones (primary follicles) and germinal centers in spleen and lymph nodes. In general, the Lyt-1 only population represents approximately 2% of spleen cells. The relative quantitative expression of Thy-1, Lyt-1, Lyt-2, and Lyt-3 changes systematically during T cell maturation. Among Lyt-1+2+3+ cells in the thymus, Thy-1 and Lyt-2 are high, whereas Lyt-1 is low. Among splenic T cells, in contrast, Thy-1 is low, Lyt-1 is high, and Lyt-2 and Lyt-3 are a little higher than in thymus. In general, Thy-1 expression is negatively correlated with Lyt-1. Thus, even among splenic and lymph node T cells subpopulations exist that tend to be either high Thy-1 and low Lyt-1 or vice versa. Lyt-2+3+ cells represent approximately 85% of thymocytes but only approximately 35% of splenic or lymph node T cells. The Lyt-2+3+ cells are found predominantly in the low Lyt-1, high Thy-1 subpopulation.

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