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.

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 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.

Loss of Normal T-Cell Subset Distribution in Myelofibrosis Is Recovered By the Immunomodulatory Effects of JAK1/2 Inhibition

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3138-3138
Author(s):  
Sanja Prijic ◽  
Taghi Manshouri ◽  
Ivo Veletic ◽  
Kate J Newberry ◽  
Ying Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytokine Production ◽  
Memory T Cells ◽  
Cell Subset ◽  
Effector Memory ◽  
Spleen Size ◽  
Effector Memory T Cells ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

Abstract Introduction: Myeloproliferative neoplasms (MPN) are clonal disorders of the hematopoietic system characterized by an excessive proliferation of myeloid cells and progressive bone marrow fibrosis. MPNs are result of an abnormal constitutive activation of the JAK/STAT signaling pathway. Ruxolitinib is the first JAK1/2 inhibitor approved for the treatment of myelofibrosis (MF), the most aggressive of MPNs. However, the beneficial effects of ruxolitinib cannot be attributed to its anticlonal activity but rather to its reduction in inflammatory cytokine production, spleen size and symptom burden. Helper (CD4+) and cytotoxic (CD8+) T-cells are key mediator elements in the adaptive immune system. Disrupted homeostasis of functionally diverse T-cell subpopulations (naïve, memory and effector) can result in abnormal cytokine production. The aim of this study was to determine the baseline T-cell subset composition in patients with MF and to monitor the immunomodulatory effects of JAK1/2 inhibition. Methods: CD4+ and CD8+T-cell subpopulations were measured in PB samples from healthy controls (n=16) and PB and BM samples from patients (n=47) with MF treated on a phase I/II clinical trial of ruxolitinib, using multiparametric flow cytometry. Subsets were immunophenotypically defined based on the cell-surface expression of CD45RO and CD62L as follows: naïve T-cells, CD45RO-CD62L+; central memory (CM), CD45RO+CD62L+; effector memory (EM), CD45RO+CD62L-; and terminally differentiated effector memory T-cells (TEM) CD45RO-CD62L-. Results: Our results showed no significant difference in the distribution of helper vs. cytotoxic T-cells between untreated MF patients and healthy subjects. Nevertheless, profound alterations in both the CD4+ and CD8+ compartments were found in MF patients. Patients with MF had significantly fewer antigen inexperienced naïve (38.7±3.1% vs. 12.9±2.0%, p<0.0001; 26.5±2.6% vs. 7.0±1.2%, p<0.0001) and central memory (23.9±1.7% vs. 6.9±0.9%, p<0.0001; 10.7±1.1% vs. 2.7±0.4%, p<0.0001) T-cells than control subjects. At the same time, terminally differentiated effector memory T-cells were significantly increased in MF patients (13.0±1.0% vs. 44.0±2.5%, p<0.0001, 26.6±2.4% vs. 58.3±2.2%, p<0.0001). To determine the effects of JAK1/2 inhibition on the T-cell subset distribution, we compared baseline (n=47) T-cell subsets with on-treatment (n=49) patient samples. Median follow-up time was 2.8 years (range: 0.2-8.0 years). We found that ruxolitinib administration increased the naïve and CM T-cells in both the CD4+ (12.9±2.0% vs. 20.1±1.4%, p=0.011; 6.9±0.9% vs. 18.3±1.2%, p<0.0001) and CD8+ populations (7.0±1.2% vs. 11.4±1.1%, p=0.02; 2.7±0.4% vs. 5.4±0.5%, p=0.0001), whereas it decreased TEM (44.0±2.5% vs. 25.5±1.7%, p<0.0001; 58.3±2.2% vs. 48.8±2.4%, p=0.0072). Remarkably, only patients who achieved a ≥50% spleen size reduction (SR) had a significant increase in naïve CD4+ (11.0±2.5% vs. 24.2±1.8%, p=0.0002, compared with 17.0±5.2% vs. 16.0±2.4%, p=0.98 for SR <50%) and CD8+ T-cells (5.4±1.3% vs. 12.3±1.5%, p=0.0036, compared with 10.4±3.2% vs. 9.3±2.3%, p=0.96 for SR <50%) during ruxolitinib treatment. Conclusions: In patientswith MF, T-cell subsets are skewed towards the effector phenotype. It has been shown that terminally differentiated effector memory T-cells are generated as a result of cytokine-driven rather than antigen-driven proliferation and differentiation stimuli. These highly efficient effector cells produce vast amounts of pro-inflammatory cytokines that account for and/or contribute to the chronic inflammatory milieu commonly found in MF. The JAK1/2 inhibitor reverses the equilibrium towards naïve T-cell phenotype to some extent, possibly contributing to the diminished cytokine production seen after JAK1/2 inhibition. This effect is more pronounced in patients with a better response, as measured by the degree of spleen size reduction. In conclusion, even though MF is a disease of the myeloid lineage, we show evidence of severe immune derangements in T-cell subpopulations. Ruxolitinib might exert its benefit for MF patients due to its modulating effect on T-cells known to produce high cytokine levels. 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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