scholarly journals Characteristics of Early Recovery of Double Negative T-Cell Subpopulations after Haploidentical Hematopoietic Stem Cell Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4589-4589
Author(s):  
Jiangying Liu ◽  
Zhilei Bian ◽  
Qiang Fu ◽  
Ying-Jun Chang ◽  
Xiao-Jun Huang
Keyword(s):  
T Cell ◽  
Prospective Study ◽  
Normal Level ◽  
Double Negative ◽  
Immune Recovery ◽  
Normal Range ◽  
Early Recovery ◽  
Hematopoietic Stem ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

Abstract Background: Immune recovery is recognized to be crucial for decreasing morbidity of the subsequent complications in patients who underwent alloHSCT. We recently compared the recoveries of T-cell subpopulations between the haploHSCT recipients with and without EBV-DNAemia and found that lower CD4/CD8 double negative T-cell (DNT) counts were significantly correlated with the increased cumulative incidence of EBV reactivation after transplantation. Multivariate analysis further showed that hampered recovery of DNT cells was an independent risk factor to predict transplant-related mortality. Based on the expression of αβ or γδ T-cell receptors, or NK cell markers, several subpopulations of DNT cells have been identified, e.g. TCR-γ/δ+DNT, TCR-α/β+DNT, NKT cells, and other cells that are incompletely characterized. Early recovery levels of DNT subsets may correlate to the occurrence of HSCT complications. Notably, reconstitution kinetics of these special T-cell subpopulations post-HSCT remains unknown. Method: A prospective study was conducted to observe the comprehensive characteristics of DNT recovery. Fifteen healthy donors and 60 consecutive patients who were diagnosed as hematological malignancy and underwent haploHSCT at our institute were included. Immnophenotyping analysis was performed to determine the recovery levels of DNT and its subpopulations including α/β+DNT, γ/δ+DNT (Vδ1+ and Vδ2+), and CD56+DNT at 30, 60, and 90 days after transplantation. Result: Percentages of total DNT, α/β+DNT, and γ/δ+DNT in recipients on day 30 were comparable with those of health donors (defined as normal range). While the percentage of total DNT significantly decreased on day 60 and day 90, percentages of α/β+DNT and γ/δ+DNT were quite stable within the 3 months after haploHSCT. Interestingly, ratio of Vδ1+/ Vδ2+ on day 30 was similar with the normal control, which was significantly reversed on day 60 and day 90. In contrast, the percentage of CD56+DNT on day 30 was 3-fold higher than the normal range, which dropped down to the normal level at 60 and 90 days. In term of the absolute numbers, all detected DNT subpopulations were hampered at 30 days post-transplantation. Only the counts of Vδ1+DNT achieved the normal level at 60 and 90 days whereas numbers of other DNT subpopulations were continuously lower during the evaluation period. The pace of Vδ2+DNT recovery was the slowest compared with others. Conclusion: Our observations give a picture of the dynamic recovery of DNT subpopulations and contribute to comprehensively understand the characteristics of immune recovery after HaploHSCT. The clinical impact of DNT-subpopulations recovery will be evaluated in the ongoing prospective study. These findings may facilitate the intervention strategies to improve the general outcome of haploHSCT recipients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Adult Renal Stem/Progenitor Cells Can Modulate T Regulatory Cells and Double Negative T Cells

2020 ◽  
Vol 22 (1) ◽  
pp. 274
Author(s):  
Claudia Curci ◽  
Angela Picerno ◽  
Nada Chaoul ◽  
Alessandra Stasi ◽  
Giuseppe De Palma ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Progenitor Cells ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Double Negative ◽  
Chronic Injury ◽  
Peripheral Blood Mononuclear ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

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.

scholarly journals Distinct CD4−CD8− (Double-Negative) Memory T-Cell Subpopulations Are Associated With Indeterminate and Cardiac Clinical Forms of Chagas Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Livia Silva Araújo Passos ◽  
Carolina Cattoni Koh ◽  
Luísa Mourão Dias Magalhães ◽  
Maria do Carmo Pereira Nunes ◽  
Kenneth John Gollob ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chagas Disease ◽  
Central Memory ◽  
Effector Memory ◽  
Double Negative ◽  
Cytokine Network ◽  
Chagas Cardiomyopathy ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

CD4−CD8− (double-negative, DN) T cells are critical orchestrators of the cytokine network associated with the pathogenic inflammatory response in one of the deadliest cardiomyopathies known, Chagas heart disease, which is caused by Trypanosoma cruzi infection. Here, studying the distribution, activation status, and cytokine expression of memory DN T-cell subpopulations in Chagas disease patients without cardiac involvement (indeterminate form—IND) or with Chagas cardiomyopathy (CARD), we report that while IND patients displayed a higher frequency of central memory, CARD had a high frequency of effector memory DN T cells. In addition, central memory DN T cells from IND displayed a balanced cytokine profile, characterized by the concomitant expression of IFN-γ and IL-10, which was not observed in effector memory DN T cells from CARD. Supporting potential clinical relevance, we found that the frequency of central memory DN T cells was associated with indicators of better ventricular function, while the frequency of effector memory DN T cells was not. Importantly, decreasing CD1d-mediated activation of DN T cells led to an increase in IL-10 expression by effector memory DN T cells from CARD, restoring a balanced profile similar to that observed in the protective central memory DN T cells. Targeting the activation of effector memory DN T cells may emerge as a strategy to control inflammation in Chagas cardiomyopathy and potentially in other inflammatory diseases where these cells play a key role.

scholarly journals CD4+/CD8+ mucosa-associated invariant T cells foster the development of endometriosis: a pilot study

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Caihua Li ◽  
Zhimin Lu ◽  
Kaihuan Bi ◽  
Kangxia Wang ◽  
Yuping Xu ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Subset ◽  
Immune Dysregulation ◽  
Double Negative ◽  
High Activation ◽  
Elisa Kit ◽  
Mait Cells ◽  
Serum Ca125 ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

Abstract Background Immune dysregulation is one of the mechanisms to promote endometriosis (EMS). Various T cell subpopulations have been reported to play different roles in the development of EMS. The mucosa-associated invariant T cell (MAIT) is an important T cell subset in the pathogenesis of various autoimmune diseases. Evidence has indicated that there are three functionally distinct MAIT subsets: CD4+, CD8+ and CD4/CD8−/− (double negative, DN) MAIT cells. Till now, the associations between endometriosis and MAIT have not been studied. Our research investigates different MAIT subpopulations in peripheral blood (PB) and peritoneal fluid (PF) from EMS patients. Methods Thirty-two EMS patients and eighteen controls were included. PB and PF were collected. Tests of cytokines in plasma and PF were performed by ELISA kit. Characterisations of MAIT were done by flow cytometry. MAIT cells have been defined as CD3 + CD161 + Vα7.2+ cells. Based on CD4 and CD8 expression, they were divided into CD8+MAIT, CD4+MAIT and DN MAIT. Results Enrichments of MAIT cells, especially CD4 and CD8 MAIT subsets were found. Moreover, CD8 MAIT cells had a high activation in the EMS group. EMS patients produced higher level of IL-8/12/17 as compared to these from controls. On the contrary, control patients exhibited an impressive upregulation of DN MAIT cells, however, these DN MAIT cells from controls showed a higher expression of PD-1. Lastly, we performed the relevance analysis, and discovered that the accumulation of PB MAIT cells positively correlated with an elevated level of serum CA125 production in EMS group. Conclusion These results suggest that different MAIT subsets play distinct roles in the progression of endometriosis.

Imbalances in T cell subpopulations in human gliomas

1988 ◽  
Vol 68 (4) ◽  
pp. 589-593 ◽  
Author(s):  
Manoj K. Bhondeley ◽  
Raj D. Mehra ◽  
Narinder K. Mehra ◽  
Ashok K. Mohapatra ◽  
Prakash N. Tandon ◽  
...  
Keyword(s):  
T Cell ◽  
Immunosuppressive Drug ◽  
Normal Range ◽  
Content Type ◽  
Fourfold Increase ◽  
T Cell Lymphopenia ◽  
Healthy Control ◽  
History Of ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

✓ The quantitation of cells bearing CD3, CD4, CD8, and B cell phenotypic markers, as well as an estimation of serum immunoglobulin (Ig)G, IgA, and IgM, was carried out in a group of 39 glioma patients with different grades of malignancy. The findings were compared with those obtained from 21 normal healthy control subjects. The analysis revealed a significant decrease both in the absolute numbers and in the percentages of circulating CD3+ (p < 0.001) and CD4+ (p < 0.001) cells, while the CD8+ and Pan B+ cells remained within the normal range irrespective of the type and grade of tumor. The CD4+:CD8+ ratio was significantly decreased in all categories of patients. The CD4 lymphopenia was also evident in 10 patients who had no history of previous immunosuppressive drug therapy (steroids and anticonvulsants) until the commencement of the study. The Ig levels were within the normal range in patients with malignant astrocytoma and glioblastoma multiforme, whereas a three- and fourfold increase in the IgM level was observed in patients with astrocytoma. It is suggested that T cell lymphopenia in glioma patients could mainly be due to a selective depletion of CD4+ cells and that it occurs principally as a reaction to the tumor.

Abnormalities of the Bone Marrow Immune Microenvironment in Patients with Prolonged Isolated Thrombocytopenia after Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4602-4602
Author(s):  
Yang Song ◽  
Yuan Kong ◽  
Min-Min Shi ◽  
Yu-Qian Sun ◽  
Yu Wang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Cd8 T Cells ◽  
Immune Microenvironment ◽  
Hematopoietic Stem ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

Abstract Background:Prolonged Isolated Thrombocytopenia (PT), is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and defined as the engraftment of all peripheral blood cell lines other than a PLT count ≤20×10E+9/L or dependence on PLT transfusions for more than 90 days after allo-HSCT. Nevertheless, the mechanisms underlying PT remain unclear. Recent studies have presumed that the mechanism of PT might be similar, at least in part, to that of Immune Thrombocytopenia (ITP). BM immune microenvironment is considered to be involved in the regulation of hematopoiesis, and also influence the production of platelets. There is growing evidence that activated CD8+ T cells in the bone marrow (BM) of patients with ITP might suppress megakaryocyte apoptosis, leading to impaired platelet production. In our previous study, we also found the deregulated T cells responses in BM were associated with ITP patients. Therefore, we hypothesized aberrant immune microenvironment may also influence the production of platelet after allo-HSCT, contributing to the occurrence of PT, so we conducted a study to analyze the alteration of T cell subpopulations and cytokines in BM micro-environment of allotransplant patients. Aims:To compare the cellular compositions and function of T cells in BM microenvironment between patients with PT and good graft function (GGF) after allo-HSCT. Methods:Using a prospective nested case-control study, the T cell subpopulations in BM were analyzed by flow cytometry in 15 patients with PT, 30 matched patients with GGF after allo-HSCT, and 15 healthy donors (HDs). The fractions of T cells, including Th1, Tc1,Th2, Tc2 ,Th17 and Treg were identified as CD3+CD8-IFN-gama+, CD3+CD8-IFN-gama+, CD3+CD8+IL4+, CD3+CD8+IL-4+, CD3+CD8-IL17A+ and CD3+CD4+CD25+Foxp3+, respectively. The levels of IFN-gama, IL-4 and IL-17A in BM plasma were detected by cytometric beads assay. Results: The demographic and clinical characteristics were similar between allo-HSCT patients with PT and those with GGF. The T cell subset analysis revealed that the proportion of CD8+ T cells in BM was higher in PT patients. The in vitro cytokine stimulated tests demonstrated a significant higher proportion of Th1 in PT patients (29.8% ±13.0% vs. 21.7%±12.2%, P=0.01), and we also found an elevated percentage of Tc1 in PT patients when compared with GGF (39.3% ±19.3% vs. 23.0% ± 14.0%, P=0.01). Meanwhile, the similar percentage of Th2 and Tc2 were found in PT patients. The type-1/ type-2 response ratio was calculated by the percentages of Th1/Th2 and Tc1/Tc2. A significant elevation in the ratio of Tc1/Tc2 (37.3 vs. 22.1 vs. 15.6, P<0.05) was observed in PT when compared with those in GGF and HDs, whereas the ratio of Th1/Th2 did not differ from GGF. Moreover, we also found the significant elevated percentage of Th17 (3.1% ±2.1% vs. 1.1%± 0.7%, P<0.01) and the similar percentage of Treg in PT patients compared with GGF, leading to a higher ratio of Th17/Treg (0.9 vs. 0.6 vs. 0.3, P<0.05). The changes of IFN-gama, IL-4 and IL-17A levels in BM plasma detected by cytometric beads assay were in accordance with the intracellular cytokine results analyzed by flow cytometry. Summary/Conclusion: Our study demonstrated that the abnormal BM immune microenvironment including the higher percentage of Th1, Tc1, and Th17 cells in patients with PT, suggesting that the dysfunction of T cells response in BM immune microenvironment may contribute to the occurrence of PT after allo-HSCT. Disclosures No relevant conflicts of interest to declare.

scholarly journals Identification of the Lymphoma-Initiating Cell Population in a T Cell Lymphoma Mouse Model Resembling Human Anaplastic Large Cell Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2213-2213
Author(s):  
Cathrin Klingeberg ◽  
Stefanie Kreutmair ◽  
Cornelius Miething ◽  
Marie Follo ◽  
Christian Peschel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Cell Population ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Double Negative ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

Abstract In 60% of anaplastic large cell lymphoma (ALCL) patients a translocation t(2;5) (p23;q35) is found, which results in NPM-ALK fusion gene expression and constitutive activation of the ALK tyrosine kinase. Immunophenotypic characterization of human ALCLs revealed highly CD30-positive cells of T- or Null-cell-origin. However, the origin of the lymphoma initiating cell population as well as NPM-ALK signal transduction in course of the disease remains unclear. In this regard, we established a retroviral murine bone marrow transplantation model resembling human ALCL. Therefore we use an inducible Cre/loxP system where NPM-ALK expression is restricted to early T cells. We infected bone marrow of Lck-Cre transgenic mice with our MSCV-Stop-NPM-ALK-IRES-EGFP vector and transplanted it into lethally irradiated recipient mice. With a latency of 4-5 months, these mice developed Thy1.2-positive lymphomas and died from neoplastic T cell infiltration of bone marrow and lymphatic organs. Immunophenotypic analysis confirmed T cell origin of the lymphomas with the characteristic high CD30 expression. Staining of the T cell subpopulations demonstrated high NPM-ALK expression in immature CD4-/CD8- double negative T cells and undifferentiated CD4+/CD8+ double positive T cells. Interestingly, FACS-staining for the proliferation marker Ki-67 as well as the activation marker CD30 revealed highest expression in the CD4-/CD8- double negative T cells. Therefore we hypothesized that the lymphoma-initiating cell must be within this early T cell population. To substantiate our hypothesis we performed secondary transplantations with sorted T cell subpopulations and indeed, only the CD4-/CD8- double negative population was able to initiate T cell lymphoma in the recipient mice. Immunophenotypic characterization of the lymphoma population of these secondary transplanted mice revealed undifferentiated T cells of all CD4/CD8 subtypes, which argues for the existence of a lymphoma initiating cell population, which can still partly differentiate. Interestingly the CD4-/CD8- double negative lymphoma population aberrantly expressed the T cell receptor alpha/beta chain, which may allow these early T cells to establish a systemic lymphoma. Further analysis of the lymphoma population showed lymphatic precursors (CLP) as well as multipotent progenitors (MMP) and haematopoetic stem cells (LSK), which suggests early bone marrow or thymic progenitor cells as the pool of the lymphoma-initiating cell population. We therefore were able to prove the existence of lymphoma initiating stem cells in a highly relevant NPM-ALK positive CD30 expressing mouse model of ALCL. Further analysis will give insides into eradication of the identified lymphoma stem cell population by clinical relevant NPM-ALK inhibitors and CD30 immunotoxins. Disclosures No relevant conflicts of interest to declare.

scholarly journals Regulatory T Cell-Enhancing Therapies to Treat Atherosclerosis

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 723
Author(s):  
Hafid Ait-Oufella ◽  
Jean-Rémi Lavillegrand ◽  
Alain Tedgui
Keyword(s):  
T Cell ◽  
Current Knowledge ◽  
Experimental Studies ◽  
Therapeutic Approaches ◽  
Coronary Patients ◽  
Cell Subpopulations ◽  
Atherosclerotic Process ◽  
T Cell Subpopulations ◽  
Disease Analysis

Experimental studies have provided strong evidence that chronic inflammation triggered by the sub-endothelial accumulation of cholesterol-rich lipoproteins in arteries is essential in the initiation and progression of atherosclerosis. Recent clinical trials highlighting the efficacy of anti-inflammatory therapies in coronary patients have confirmed that this is also true in humans Monocytes/macrophages are central cells in the atherosclerotic process, but adaptive immunity, through B and T lymphocytes, as well as dendritic cells, also modulates the progression of the disease. Analysis of the role of different T cell subpopulations in murine models of atherosclerosis identified effector Th1 cells as proatherogenic, whereas regulatory T cells (Tregs) have been shown to protect against atherosclerosis. For these reasons, better understanding of how Tregs influence the atherosclerotic process is believed to provide novel Treg-targeted therapies to combat atherosclerosis. This review article summarizes current knowledge about the role of Tregs in atherosclerosis and discusses ways to enhance their function as novel immunomodulatory therapeutic approaches against cardiovascular disease.

T-cell subpopulations and colorectal cancer

1990 ◽  
Vol 33 (5) ◽  
pp. 367-369
Author(s):  
Andrea Ferrara ◽  
Marvin M. McMillen ◽  
Garth H. Ballantyne
Keyword(s):  
Colorectal Cancer ◽  
T Cell ◽  
Cell Subpopulations ◽  
T Cell Subpopulations
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