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 ◽  
...  

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.

2017 ◽  
Vol 114 (43) ◽  
pp. E9056-E9065 ◽  
Author(s):  
Dorien Van hede ◽  
Barbara Polese ◽  
Chantal Humblet ◽  
Anneke Wilharm ◽  
Virginie Renoux ◽  
...  

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.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 229.2-229
Author(s):  
B. Dreo ◽  
B. Prietl ◽  
S. Kofler ◽  
H. Sourij ◽  
A. Lackner ◽  
...  

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


Author(s):  
Martina Formentini ◽  
Ana Navas ◽  
Fakhri Hassouneh ◽  
Nelson Lopez-Sejas ◽  
Corona Alonso ◽  
...  

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.


Rheumatology ◽  
2021 ◽  
Author(s):  
Anne Filleron ◽  
Tu Anh Tran ◽  
Audrey Hubert ◽  
Alexia Letierce ◽  
Guillaume Churlaud ◽  
...  

Abstract Objectives Behçet disease (BD) is a chronic systemic inflammatory disorder of unknown aetiology. The aim of this study was to determine the orientation of T cell subpopulations in pediatric BD and more precisely to look for a regulatory T lymphocytes (Tregs)/Th17 imbalance. Methods T cell subpopulations were analyzed by flow cytometry in the peripheral blood of pediatric patients with acute (aBD, n = 24), remitting (rBD, n = 12) BD, and in healthy controls (HC, n = 24). Tregs (CD4+CD25hiCD127-/loFoxp3+), activated Tregs (GITR, LAP, CTLA-4, and HLA-DR expression), CD4+ and CD8+ T cells producing interferon-g (Th1 and Tc1) or interleukin (IL)-17 (Th17 and Tc17) under polyclonal (OKT3/IL-2) or antigenic (Streptococcus sanguis KTH-1 peptides and HSP-60) stimulation, were numerated. Results Th17 (1.9 and 5.1 fold) and Tc17 (4.0 and 2.0 fold) frequency under mitogenic stimulation was significantly increased in aBD and rBD patients as compared with HC. Th17 frequency under antigenic stimulation was also higher in patients than in HC. The percentage and number of Tregs and activated Tregs in patients and in HC were similar. However, when Tregs were removed, antigen-driven differentiation into Th1 and Th17 was significantly boosted in BD but not in HC CD4+T cells. Conclusion There is a bias toward a Th17 polarization in acute and remitting BD children. Although we did not observe an increase in the number of Tregs in these patients, their Tregs limit CD4+T cell differentiation into Th1 and Th17 cells. Thus, in pediatric BD, Tregs seem to incompletely counterbalance a Th17 orientation of the helper T cell response.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4278-4278
Author(s):  
Peter Brinkrolf ◽  
Silke Landmeier ◽  
Bianca Altvater ◽  
Sibylle Pscherer ◽  
Annegret Rosemann ◽  
...  

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.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Premrutai Thitilertdecha ◽  
Ladawan Khowawisetsut ◽  
Palanee Ammaranond ◽  
Poonsin Poungpairoj ◽  
Varangkana Tantithavorn ◽  
...  

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.


2000 ◽  
Vol 7 (6) ◽  
pp. 953-959 ◽  
Author(s):  
Zhong Chen Kou ◽  
Joshua S. Puhr ◽  
Mabel Rojas ◽  
Wayne T. McCormack ◽  
Maureen M. Goodenow ◽  
...  

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.


1980 ◽  
Vol 152 (2) ◽  
pp. 280-295 ◽  
Author(s):  
J A Ledbetter ◽  
R V Rouse ◽  
H S Micklem ◽  
L A Herzenberg

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.


2021 ◽  
Vol 12 ◽  
pp. 204062232098672
Author(s):  
Hong-Qing Niu ◽  
Chenrui Yuan ◽  
Chenglan Yan ◽  
Na Li ◽  
Yuan-Sheng Lei ◽  
...  

Aims: CD4+ T cells play crucial roles as both mediators and regulators of the pathogenesis of rheumatoid arthritis (RA). However, the characteristics of CD4+ T cell subpopulations in the earliest stage of RA development remain unclear. Hence, we determined the proportions and absolute counts of circulating CD4+ T cell subsets in patients with seropositive undifferentiated arthritis (SUA), the early and preclinical stage of RA. Methods: Peripheral blood samples and clinical information were collected from 177 patients with SUA, 104 patients with RA, and 120 healthy controls. All patients were newly diagnosed and untreated. Proportions and absolute counts of CD4+ T cell subpopulations were determined by flow cytometric analysis. Results: In patients with SUA, percentages and absolute counts of circulating regulatory T (Treg) cells were decreased significantly and Th17/Treg cell ratios were abnormally increased, whereas Th17 cell numbers were similar to those in healthy controls. In addition, sex-based differences in circulating Treg cells were observed, with female SUA patients having lower proportions and absolute counts of Treg cells than those in males. Moreover, female patients with SUA had higher erythrocyte sedimentation rates and 28-joint Disease Activity Scores than those in males. Conclusion: Immune tolerance deficiency resulting from an abnormal reduction in circulating Treg cells might be the most crucial immunological event in the earliest stage of RA. The sex-specific disparity in Treg cells should also be considered for immunoregulatory and preventive strategies targeting early RA.


2020 ◽  
Vol 22 (1) ◽  
pp. 274
Author(s):  
Claudia Curci ◽  
Angela Picerno ◽  
Nada Chaoul ◽  
Alessandra Stasi ◽  
Giuseppe De Palma ◽  
...  

Adult Renal Stem/Progenitor Cells (ARPCs) have been recently identified in the human kidney and several studies show their active role in kidney repair processes during acute or chronic injury. However, little is known about their immunomodulatory properties and their capacity to regulate specific T cell subpopulations. We co-cultured ARPCs activated by triggering Toll-Like Receptor 2 (TLR2) with human peripheral blood mononuclear cells for 5 days and 15 days and studied their immunomodulatory capacity on T cell subpopulations. We found that activated-ARPCs were able to decrease T cell proliferation but did not affect CD8+ and CD4+ T cells. Instead, Tregs and CD3+ CD4- CD8- double-negative (DN) T cells decreased after 5 days and increased after 15 days of co-culture. In addition, we found that PAI1, MCP1, GM-CSF, and CXCL1 were significantly expressed by TLR2-activated ARPCs alone and were up-regulated in T cells co-cultured with activated ARPCs. The exogenous cocktail of cytokines was able to reproduce the immunomodulatory effects of the co-culture with activated ARPCs. These data showed that ARPCs can regulate immune response by inducing Tregs and DN T cells cell modulation, which are involved in the balance between immune tolerance and autoimmunity.


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