scholarly journals CD8 + T‐cell senescence and skewed lymphocyte subsets in young Dyskeratosis Congenita patients with PARN and DKC1 mutations

2020 ◽  
Vol 34 (9) ◽  
Author(s):  
Ting Zeng ◽  
Ge Lv ◽  
Xuemei Chen ◽  
Lu Yang ◽  
Lina Zhou ◽  
...  
Keyword(s):  
T Cell ◽  
Lymphocyte Subsets ◽  
Cd8 T Cell ◽  
Dyskeratosis Congenita ◽  
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 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 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 Lymphocyte subset analysis to evaluate the prognosis of HIV-negative patients with pneumocystis pneumonia

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fan Jin ◽  
Jing Xie ◽  
Huan-ling Wang
Keyword(s):  
T Cell ◽  
Cell Count ◽  
Lymphocyte Subsets ◽  
Nk Cell ◽  
Cd8 T Cell ◽  
Pneumocystis Pneumonia ◽  
Lymphocyte Subset ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Hiv Negative

Abstract Objectives We analysed the peripheral blood lymphocyte subsets of human immunodeficiency virus (HIV)-negative patients infected with pneumocystis pneumonia (PCP) to determine the relationships between the levels of different types of lymphocytes and the prognosis of patients. Methods We retrospectively reviewed HIV-negative patients with PCP diagnosed in our department. All the eligible patients underwent lymphocyte subset analysis on admission. Results A total of 88 HIV-negative PCP patients were enrolled in the study. In univariate analyses, low CD4+ T cell count, low CD8+ T cell count, and low natural killer cell (NK cell) count were associated with higher in-hospital mortality. CD8+ T cell count ≤300/μL was found to be an independent risk factor for poor prognosis in multivariate logistical regression analysis (p = 0.015, OR = 11.526, 95% CI = 1.597–83.158). Although low CD4+ T cell and NK cell counts were not independent risk factors, the mortality rates of PCP patients decreased as the CD4+ T cell and NK cell counts increased. Conclusion The immune process of Pneumocystis jirovecii infection is complex but important. We propose that lymphocyte subsets could give clinicians a better understanding of patient immune status, helping with the early identification of potentially lethal infections and treatment decision making, such as adjusting the immunosuppressive regimen and choosing an appropriate patient monitoring level.

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.

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