scholarly journals Comparative analyses of regulatory T cell subsets in patients with hepatocellular carcinoma: A crucial role of CD25−FOXP3−T cells

2012 ◽  
Vol 131 (11) ◽  
pp. 2573-2583 ◽  
Author(s):  
Naruyasu Kakita ◽  
Tatsuya Kanto ◽  
Ichiyo Itose ◽  
Shoko Kuroda ◽  
Michiyo Inoue ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cell ◽  
Crucial Role ◽  
T Cell Subsets ◽  
Comparative Analyses

scholarly journals Antigen-Specific T Cells and Cytokines Detection as Useful Tool for Understanding Immunity against Zoonotic Infections

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Annalisa Agnone ◽  
Alessandra Torina ◽  
Gesualdo Vesco ◽  
Sara Villari ◽  
Fabrizio Vitale ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Crucial Role ◽  
T Cell Subsets ◽  
Host Immune Responses ◽  
Zoonotic Infections ◽  
Immunological Mechanisms

Zoonoses include a broad range of diseases, that are becoming of great interest, due to the climate changing, that cause the adaptation of vectors to new niches and environments. Host immune responses play a crucial role in determining the outcome of infections, as documented by expansion of antigen-specific T cells during several zoonotic infections. Thus, understanding of the contribution of antigen-specific T-cell subsets in the host immune response is a powerful tool to evaluate the different immunological mechanisms involved in zoonotic infections and for the development of effective vaccines. In this paper we discuss the role of T cells in some eukaryotic and prokaryotic infectious models.

scholarly journals The role of unconventional T cells in COVID-19

2021 ◽  
Author(s):  
Kristen Orumaa ◽  
Margaret R. Dunne
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Treatment Strategies ◽  
Γδ T Cells ◽  
Protective Role ◽  
T Cell Subsets ◽  
Viral Immunity ◽  
Mait Cells

AbstractCOVID-19 is a respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first documented in late 2019, but within months, a worldwide pandemic was declared due to the easily transmissible nature of the virus. Research to date on the immune response to SARS-CoV-2 has focused largely on conventional B and T lymphocytes. This review examines the emerging role of unconventional T cell subsets, including γδ T cells, invariant natural killer T (iNKT) cells and mucosal associated invariant T (MAIT) cells in human SARS-CoV-2 infection.Some of these T cell subsets have been shown to play protective roles in anti-viral immunity by suppressing viral replication and opsonising virions of SARS-CoV. Here, we explore whether unconventional T cells play a protective role in SARS-CoV-2 infection as well. Unconventional T cells are already under investigation as cell-based immunotherapies for cancer. We discuss the potential use of these cells as therapeutic agents in the COVID-19 setting. Due to the rapidly evolving situation presented by COVID-19, there is an urgent need to understand the pathogenesis of this disease and the mechanisms underlying its immune response. Through this, we may be able to better help those with severe cases and lower the mortality rate by devising more effective vaccines and novel treatment strategies.

scholarly journals Thymic Regulatory T Cell Development: Role of Signalling Pathways and Transcription Factors

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Mark Engel ◽  
Tom Sidwell ◽  
Ajithkumar Vasanthakumar ◽  
George Grigoriadis ◽  
Ashish Banerjee
Keyword(s):  
T Cells ◽  
Transcription Factors ◽  
T Cell ◽  
Regulatory T Cells ◽  
Immune Tolerance ◽  
Regulatory T Cell ◽  
T Cell Development ◽  
Signalling Pathways ◽  
Treg Development

Regulatory T cells (Tregs) are a subset of CD4 T cells that are key mediators of immune tolerance. Most Tregs develop in the thymus. In this review we summarise recent findings on the role of diverse signalling pathways and downstream transcription factors in thymic Treg development.

scholarly journals Global immune characterization of HBV/HCV-related hepatocellular carcinoma identifies macrophage and T-cell subsets associated with disease progression

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Guohe Song ◽  
Yang Shi ◽  
Meiying Zhang ◽  
Shyamal Goswami ◽  
Saifullah Afridi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Immune Cells ◽  
Immune Cell ◽  
T Cell Subsets ◽  
M2 Macrophage ◽  
Advanced Hcc ◽  
Immune Cell Subsets

AbstractDiverse immune cells in the tumor microenvironment form a complex ecosystem, but our knowledge of their heterogeneity and dynamics within hepatocellular carcinoma (HCC) still remains limited. To assess the plasticity and phenotypes of immune cells within HBV/HCV-related HCC microenvironment at single-cell level, we performed single-cell RNA sequencing on 41,698 immune cells from seven pairs of HBV/HCV-related HCC tumors and non-tumor liver tissues. We combined bio-informatic analyses, flow cytometry, and multiplex immunohistochemistry to assess the heterogeneity of different immune cell subsets in functional characteristics, transcriptional regulation, phenotypic switching, and interactions. We identified 29 immune cell subsets of myeloid cells, NK cells, and lymphocytes with unique transcriptomic profiles in HCC. A highly complex immunological network was shaped by diverse immune cell subsets that can transit among different states and mutually interact. Notably, we identified a subset of M2 macrophage with high expression of CCL18 and transcription factor CREM that was enriched in advanced HCC patients, and potentially participated in tumor progression. We also detected a new subset of activated CD8+ T cells highly expressing XCL1 that correlated with better patient survival rates. Meanwhile, distinct transcriptomic signatures, cytotoxic phenotypes, and evolution trajectory of effector CD8+ T cells from early-stage to advanced HCC were also identified. Our study provides insight into the immune microenvironment in HBV/HCV-related HCC and highlights novel macrophage and T-cell subsets that could be further exploited in future immunotherapy.

scholarly journals Conventional CD4+CD25- and Regulatory CDCD4+25+ t Cells Have Opposite Effects on Progenitor Cells and Hematopoietic Reconstitution Following Stem Cell Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 654-654
Author(s):  
Antonia MS Mueller ◽  
Jessica Poyser ◽  
Holbrook E Kohrt ◽  
Judith A Shizuru
Keyword(s):  
Cell Cycle ◽  
T Cells ◽  
T Cell ◽  
Cell Transplantation ◽  
Immune Cells ◽  
T Cell Subsets ◽  
Mixed Chimerism ◽  
Allogeneic Hct ◽  
Hematopoietic Reconstitution

Abstract The bone marrow (BM) is a complex microsystem to support lifelong blood production. At steady-state most hematopoietic stem cells (HSC) are quiescent. However, in situations of increased demand, their activation is triggered by an array of signals, such as cytokines. Following hematopoietic cell transplantation (HCT) in the phase of hematopoietic reconstitution maximal blood production is needed. In an HCT donor HSC are given together with immune cells in the belief that T cells support HSC engraftment and regeneration of the blood system. Yet, states of immune mediated BM insufficiency, hypoplasia, and cytopenias are often observed. Moreover, with increased use of reduced intensity conditioning (RIC) engraftment failure has reemerged as a serious problem. Here, we studied the effects of distinct T cell subsets on hematopoietic reconstitution following HCT; specifically, we examined how conventional CD4+CD25- T cells (CD4conv) vs regulatory T cells (CD4+CD25+, Treg) modify the BM environment and influence donor-HSC activity and engraftment. We used minor-mismatched mouse models, non-myeloablative total body irradiation (TBI) conditioning and transplantations of purified HSC (KTLS; cKit+Thy1.1loLin–Sca-1+) plus selected T cell subsets. Recipients of HSC, HSC+Treg or HSC+CD8+ - but not HSC+CD4conv- demonstrated prompt donor engraftment with mixed chimerism in all lineages. Transplantation of HSC+Treg resulted in significantly faster lymphocyte recovery and higher levels of donor chimerism compared with recipients of HSC, HSC+CD8+ or HSC+CD4conv. Particularly B-cell regeneration was markedly higher in HSC+Treg-recipients compared with all other groups. In contrast, (B-) lymphopoiesis was severely impaired in recipients of HSC+CD4conv; when lymphocytes recovered eventually they were of host type. Moreover, in BM and spleens of HSC+CD4conv recipients pronounced hypocellularity was observed. This suppression of hematopoiesis was due to IFNg secretion of donor CD4conv cells, which were activated by dendritic cells via IL-12. High cytokine levels (of both IL-12 and IFNg) were only detectable in the BM (and not the spleen) of HSC+CD4conv recipients, where they resulted in an arrest of early hematopoiesis at the stage of short-term HSC and decreased cell-cycle activity within the progenitor compartment. As a consequence more mature multipotent progenitors were lacking. The key role of IFNg in halting hematopoietic maturation was confirmed by using CD4conv cells from IFNg-/- mice, which had no suppressive effects on BM cellularity and maturation of blood cells; rather, recipients of HSC+IFNg-/-CD4conv cells had equivalent cell numbers and subset distributions as mice given HSC alone. We hypothesized that differences of hematopoietic regeneration and donor engraftment relate to cell cycle activity of HSC in presence of CD4conv vs Tregs. To study the influence of these CD4-subsets on HSC cycling in more detail FACS-purified Treg vs CD4conv cells were infused into congenic mice following low-dose TBI-stimulation. In fact, on d+8 post-infusion HSC in the BM of Treg-recipients had increased cell-cycling activity in long-term-HSC and multipotent-progenitor fractions compared with mice given CD4conv cells or radiation only. These data lead us to speculate that Tregs promote, directly or indirectly, HSC proliferation; in the context of an allogeneic HCT this increased cycling of host HSC my open-up the niche space required to allow donor HSC to engraft. In contrast, CD4convinhibited HSC cycling activity, resulting in BM hypoplasia and cytopenias; at the same time donor HSC engraftment was impaired due to HSC-niche occupation by quiescent host HSC. Our findings underscore the critical role of T cells in regulating hematopoiesis under physiologic conditions and even more following allogeneic HCT. While donor T cells are generally believed to improve regeneration of the blood post-HCT and to be required to overcome host barriers, our data suggest Treg facilitate engraftment and hematopoiesis by increasing HSC cycling-activity and thereby making marrow sites available. CD4conv appear to have the opposite effect, resulting in decreased HSC proliferation and maturation - thus occupation of HSC niches. Our studies are of particular relevance to allogeneic HCT settings using RIC, where host HSC persist and grafts can be rejected by residual host immune cells. Disclosures No relevant conflicts of interest to declare.

scholarly journals Elevated coinhibitory molecule TIGIT mediates T cell exhaustion in septic patients

2021 ◽  
Author(s):  
Yini Sun ◽  
Renyu Ding ◽  
Yukun Chang ◽  
Jiuming Li ◽  
Xiaochun Ma
Keyword(s):  
T Cells ◽  
T Cell ◽  
Crucial Role ◽  
Cell Function ◽  
Inflammatory Responses ◽  
Ex Vivo ◽  
Healthy Controls ◽  
T Cell Exhaustion ◽  
Cell Exhaustion

Abstract Background: Sepsis-induced T cell exhaustion that is characterized by upregulated coinhibitory molecules and decreased cytokines release plays a crucial role in the immunosuppression during sepsis. Although PD-1 has shown a promising target to interfere with T cells dysfunction, the role of other coinhibitory receptors in sepsis remains largely elusive. Recently, it has been demonstrated that the coinhibitory molecule TIGIT more reliably identified exhausted T cells than PD-1. The aim of the study was to identify the expression of TIGIT on lymphocytes and the crucial role of TIGIT in modulating T cell function in septic patients. Methods: Twenty-five patients with sepsis and seventeen healthy controls were prospectively enrolled. Peripheral blood was obtained from septic patients within 24 hours after diagnosis of sepsis, as were healthy controls. TIGIT and other coinhibitory/costimulatory molecules expression on lymphocyte subsets was quantitated by flow cytometry. The relationship between TIGIT expression and clinical parameters was simultaneously evaluated. The function T cell from septic patients was assayed via stimulated cytokine secretion. Ex vivo functional assays were also conducted.Results: In the early stage of sepsis, patients exhibited higher levels of TIGIT on T cells relative to healthy donors, especially in the septic shock patients. Elevated frequencies of TIGIT + T cells positively correlated with the severity of organ failure and inflammatory responses in septic patients. TIGIT + T cells expressed higher levels of PD-1 and lower CD226. Further, elevated expression of TIGIT inhibited the release of cytokines including TNF, IFN-γ and IL-2 by CD4 + and CD8 + T cells. Strikingly, ex vivo blockade of TIGIT using anti-TIGIT antibody restored the frequencies of cytokine-producing T cells. Conclusions: These data illustrate TIGIT as a novel marker of exhausted T cells and suggest TIGIT may be a novel immunotherapeutic target during sepsis.

scholarly journals A possible role of immunopathogenesis in COVID-19 progression

2020 ◽  
Author(s):  
Moritz Anft ◽  
Krystallenia Paniskaki ◽  
Arturo Blazquez-Navarro ◽  
Adrian Doevelaar ◽  
Felix S. Seibert ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Humoral Immunity ◽  
Viral Infections ◽  
Cell Subset ◽  
T Cell Response ◽  
T Cell Subsets ◽  
Clear Correlation

AbstractBackgroundThe efficacy of the humoral and cellular immunity determines the outcome of viral infections. An appropriate immune response mediates protection, whereas an overwhelming immune response has been associated with immune-mediated pathogenesis in viral infections. The current study explored the general and SARS-CoV-2 specific cellular and humoral immune status in patients with different COVID-19 severities.MethodsIn this prospective study, we included 53 patients with moderate, severe, and critical COVID-19 manifestations comparing their quantitative, phenotypic, and functional characteristics of circulating immune cells, SARS-CoV-2 antigen specific T-cells, and humoral immunity.ResultsSignificantly diminished frequencies of CD8+T-cells, CD4+ and CD8+T-cell subsets with activated differentiated memory/effector phenotype and migratory capacity were found in circulation in patients with severe and/or critical COVID-19 as compared to patients with moderate disease. Importantly, the improvement of the clinical courses from severe to moderate was accompanied by an improvement in the T-cell subset alterations. Furthermore, we surprisingly observed a detectable SARS-CoV-2-reactive T-cell response in all three groups after stimulation with SARS-CoV-2 S-protein overlapping peptide pool already at the first visit. Of note, patients with a critical COVID-19 demonstrated a stronger response of SARS-CoV-2-reactive T-cells producing Th1 associated inflammatory cytokines. Furthermore, clear correlation between antibody titers and SARS-CoV-2-reactive CD4+ frequencies underscore the role of specific immunity in disease progression.ConclusionOur data demonstrate that depletion of activated memory phenotype circulating T-cells and a strong SARS-CoV-2-specific cellular and humoral immunity are associated with COVID-19 disease severity. This counter-intuitive finding may have important implications for diagnostic, therapeutic and prophylactic COVID-19 management.

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