scholarly journals Infectious Complications Predict Premature CD8+ T-cell Senescence in CD40 Ligand-Deficient Patients

2021 ◽  
Author(s):  
Junghee J. Shin ◽  
Jason Catanzaro ◽  
Jennifer R. Yonkof ◽  
Ottavia Delmonte ◽  
Keith Sacco ◽  
...  
Keyword(s):  
T Cell ◽  
Cd8 T Cell ◽  
Cd40 Ligand ◽  
Infectious Complications ◽  
Cell Senescence ◽  
T Cell Senescence

scholarly journals Accelerated Progression of Disseminated Coccidioidomycosis Following SARS-CoV-2 Infection: A Case Report

2021 ◽  
Author(s):  
Daniel S Krauth ◽  
Christina M Jamros ◽  
Shayna C Rivard ◽  
Niels H Olson ◽  
Ryan C Maves
Keyword(s):  
Immune Response ◽  
Case Report ◽  
T Cell ◽  
Cellular Response ◽  
Cd8 T Cell ◽  
Host Immune Response ◽  
Cell Senescence ◽  
Functional Exhaustion ◽  
T Cell Senescence

ABSTRACT We describe a patient with subclinical coccidioidomycosis who experienced rapid disease dissemination shortly after SARS-CoV-2 infection, suggesting host immune response dysregulation to coccidioidomycosis by SARS-CoV-2. We hypothesize that disrupted cell-mediated signaling may result after SARS-CoV-2 infection leading to functional exhaustion and CD8+ T-cell senescence with impairment in host cellular response to Coccidioides infection.

scholarly journals Impact of cART on CD8+T cell senescence: the ANRS EP45-aging study

2016 ◽  
Vol 2 ◽  
pp. 33-34
Author(s):  
Olivia Zaegel-Faucher ◽  
Corinne Nicolino-Brunet ◽  
Elisabeth Jouve ◽  
Jacques Reynes ◽  
Pierre Dellamonica ◽  
...  
Keyword(s):  
T Cell ◽  
Cd8 T Cell ◽  
Cell Senescence ◽  
Aging Study ◽  
T Cell Senescence

scholarly journals CD8+ T CELL SENESCENCE IS A DISTINCT IMMUNOLOGICAL STATE THAT IDENTIFIES LONG-TERM RENAL TRANSPLANT RECIPIENTS AT INCREASED RISK OF FUTURE MALIGNANCY

2020 ◽  
Vol 104 (S3) ◽  
pp. S106-S106
Author(s):  
Matthew J. Bottomley ◽  
Suzanne Bezstarosti ◽  
Eleni Ieremiah ◽  
Joanna Hester ◽  
Fadi Issa ◽  
...  
Keyword(s):  
T Cell ◽  
Renal Transplant ◽  
Cd8 T Cell ◽  
Cell Senescence ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Increased Risk ◽  
T Cell Senescence

scholarly journals Senescent Tumor CD8+ T Cells: Mechanisms of Induction and Challenges to Immunotherapy

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2828
Author(s):  
Wei Liu ◽  
Paweł Stachura ◽  
Haifeng C. Xu ◽  
Sanil Bhatia ◽  
Arndt Borkhardt ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
Cell Senescence ◽  
Cellular Processes ◽  
State Present ◽  
T Cell Senescence

The inability of tumor-infiltrating T lymphocytes to eradicate tumor cells within the tumor microenvironment (TME) is a major obstacle to successful immunotherapeutic treatments. Understanding the immunosuppressive mechanisms within the TME is paramount to overcoming these obstacles. T cell senescence is a critical dysfunctional state present in the TME that differs from T cell exhaustion currently targeted by many immunotherapies. This review focuses on the physiological, molecular, metabolic and cellular processes that drive CD8+ T cell senescence. Evidence showing that senescent T cells hinder immunotherapies is discussed, as are therapeutic options to reverse T cell senescence.

scholarly journals The Evolving Role of CD8+CD28− Immunosenescent T Cells in Cancer Immunology

2019 ◽  
Vol 20 (11) ◽  
pp. 2810 ◽  
Author(s):  
Wei X. Huff ◽  
Jae Hyun Kwon ◽  
Mario Henriquez ◽  
Kaleigh Fetcko ◽  
Mahua Dey
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Costimulatory Molecule ◽  
Tumor Immunotherapy ◽  
Cd8 T Cell ◽  
Cell Senescence ◽  
Cell Dysfunction ◽  
T Cell Dysfunction ◽  
T Cell Senescence

Functional, tumor-specific CD8+ cytotoxic T lymphocytes drive the adaptive immune response to cancer. Thus, induction of their activity is the ultimate aim of all immunotherapies. Success of anti-tumor immunotherapy is precluded by marked immunosuppression in the tumor microenvironment (TME) leading to CD8+ effector T cell dysfunction. Among the many facets of CD8+ T cell dysfunction that have been recognized—tolerance, anergy, exhaustion, and senescence—CD8+ T cell senescence is incompletely understood. Naïve CD8+ T cells require three essential signals for activation, differentiation, and survival through T-cell receptor, costimulatory receptors, and cytokine receptors. Downregulation of costimulatory molecule CD28 is a hallmark of senescent T cells and increased CD8+CD28− senescent populations with heterogeneous roles have been observed in multiple solid and hematogenous tumors. T cell senescence can be induced by several factors including aging, telomere damage, tumor-associated stress, and regulatory T (Treg) cells. Tumor-induced T cell senescence is yet another mechanism that enables tumor cell resistance to immunotherapy. In this paper, we provide a comprehensive overview of CD8+CD28− senescent T cell population, their origin, their function in immunology and pathologic conditions, including TME and their implication for immunotherapy. Further characterization and investigation into this subset of CD8+ T cells could improve the efficacy of future anti-tumor immunotherapy.

Differential regulation of CD8+ T cell senescence in mice and men

2001 ◽  
Vol 121 (1-3) ◽  
pp. 69-76 ◽  
Author(s):  
Arne N Akbar ◽  
Maria Vieira D Soares ◽  
Fiona J Plunkett ◽  
Mike Salmon
Keyword(s):  
T Cell ◽  
Cd8 T Cell ◽  
Differential Regulation ◽  
Cell Senescence ◽  
T Cell Senescence

scholarly journals hPMSCs protects against D-galactose-induced oxidative damage of CD4+ T cells through activating Akt-mediated Nrf2 antioxidant signaling 

2020 ◽  
Author(s):  
Yanlian Xiong ◽  
Yueming Wang ◽  
Jiashen Zhang ◽  
Nannan Zhao ◽  
Hengchao Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nuclear Translocation ◽  
Cell Senescence ◽  
Antioxidant Defenses ◽  
Control Group ◽  
Akt Inhibitor ◽  
Gsk 3Β ◽  
T Cell Senescence

Abstract Background: Mesenchymal stem cells (MSCs) was considered as regenerative therapeutic approach in both acute and chronic diseases. However, whether MSCs regulate the antioxidant metabolism of CD4+ T cells and weaken immunosenescence remains unclear. Here, we reported the protective effects of hPMSCs in aging-related CD4+ T cell senescence and identified the underlying mechanisms using a D-gal induced mouse aging model.Methods: In vivo study, 40 male C57BL/6 mice (8 weeks) were randomly divided into four groups: control group, D-gal group, hPMSC group and PBS group. In in vitro experiment, human naive CD4+ T (CD4CD45RA) cells were prepared using a naive CD4+ T cell isolation kit II and pretreated with the Akt inhibitor LY294002 and Nrf2 inhibitor ML385. Then, isolated naive CD4+ T cell were cocultured with hPMSCs for 72 h in the absence or presence of anti-CD3/CD28 Dynabeads and IL-2 as a mitogenic stimulus. Intracellular ROS changes were detected by flow cytometry. The activities of the antioxidant enzymes superoxide dismutase, glutathione peroxidase and catalase were measured by colorimetric analysis. The senescent T cells were detected SA-β-gal stain. The expression of aging related proteins were detected by Western blotting, RT-PCR and confocal microscopy.Results: We found that hPMSC treatment markedly decreased the ROS level, SA-β-gal positive cells number, senescence-associated secretory phenotype (IL-6 and OPN) expression and aging-related protein (P16 and P21) expression in senescent CD4+ T cells. Furthermore, hPMSC treatment effectively upregulated Nrf2 nuclear translocation and the expression of downstream target genes (HO-1, CAT, GCLC and NQO1) in senescent CD4+ T cells. Moreover, in vitro studies revealed that hPMSCs attenuated CD4+ T cell senescence by upregulating the Akt/GSK-3β/Fyn pathway to activate Nrf2 functions. Conversely, the antioxidant effects of hPMSCs were blocked by the Akt inhibitor LY294002 and Nrf2 inhibitor ML385 in senescent CD4+ T cells.Conclusions: Our results indicate that hPMSCs attenuate D-gal induced CD4+ T cell senescence by activating Nrf2-mediated antioxidant defenses and that upregulation of Nrf2 by hPMSCs is regulated via the Akt/GSK-3β/Fyn pathway.

scholarly journals Generation of Human CD8 T Regulatory Cells by CD40 Ligand–activated Plasmacytoid Dendritic Cells

2002 ◽  
Vol 195 (6) ◽  
pp. 695-704 ◽  
Author(s):  
Michel Gilliet ◽  
Yong-Jun Liu
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Transforming Growth Factor ◽  
Cd8 T Cell ◽  
Cd40 Ligand ◽  
Plasmacytoid Dendritic Cells ◽  
Target Cells ◽  
Ifn Γ

Although CD8 T cell–mediated immunosuppression has been a well-known phenomenon during the last three decades, the nature of primary CD8 T suppressor cells and the mechanism underlying their generation remain enigmatic. We demonstrated that naive CD8 T cells primed with allogeneic CD40 ligand–activated plasmacytoid dendritic cells (DC)2 differentiated into CD8 T cells that displayed poor secondary proliferative and cytolytic responses. By contrast, naive CD8 T cells primed with allogeneic CD40 ligand–activated monocyte-derived DCs (DC1) differentiated into CD8 T cells, which proliferated to secondary stimulation and killed allogeneic target cells. Unlike DC1-primed CD8 T cells that produced large amounts of interferon (IFN)-γ upon restimulation, DC2-primed CD8 T cells produced significant amounts of interleukin (IL)-10, low IFN-γ, and no IL-4, IL-5, nor transforming growth factor (TGF)-β. The addition of anti–IL-10–neutralizing monoclonal antibodies during DC2 and CD8 T cell coculture, completely blocked the generation of IL-10–producing anergic CD8 T cells. IL-10–producing CD8 T cells strongly inhibit the allospecific proliferation of naive CD8 T cells to monocytes, and mature and immature DCs. This inhibition was mediated by IL-10, but not by TGF-β. IL-10–producing CD8 T cells could inhibit the bystander proliferation of naive CD8 T cells, provided that they were restimulated nearby to produce IL-10. IL-10–producing CD8 T cells could not inhibit the proliferation of DC1-preactivated effector T cells. This study demonstrates that IL-10–producing CD8 T cells are regulatory T cells, which provides a cellular basis for the phenomenon of CD8 T cell–mediated immunosuppression and suggests a role for plasmacytoid DC2 in immunological tolerance.

Sign in / Sign up

Export Citation Format

Share Document