Faculty Opinions recommendation of PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression.

2006 ◽  
Author(s):  
Luis J Montaner
Keyword(s):  
T Cells ◽  
T Cell ◽  
Disease Progression ◽  
T Cell Exhaustion ◽  
Cell Exhaustion

PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression

Nature ◽  
2006 ◽  
Vol 443 (7109) ◽  
pp. 350-354 ◽  
Author(s):  
Cheryl L. Day ◽  
Daniel E. Kaufmann ◽  
Photini Kiepiela ◽  
Julia A. Brown ◽  
Eshia S. Moodley ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Disease Progression ◽  
T Cell Exhaustion ◽  
Cell Exhaustion

scholarly journals Inverted CD8 T-Cell Exhaustion and Co-Stimulation Marker Balance Differentiate Aviremic HIV-2-Infected From Seronegative Individuals

2021 ◽  
Vol 12 ◽  
Author(s):  
Lydia Scharf ◽  
Christina B. Pedersen ◽  
Emil Johansson ◽  
Jacob Lindman ◽  
Lars R. Olsen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Disease Progression ◽  
Cd8 T Cells ◽  
Therapy Monitoring ◽  
Expression Patterns ◽  
Cd8 T Cell ◽  
T Cell Exhaustion ◽  
Cell Exhaustion ◽  
Hiv 1

HIV-2 is less pathogenic compared to HIV-1. Still, disease progression may develop in aviremic HIV-2 infection, but the driving forces and mechanisms behind such development are unclear. Here, we aimed to reveal the immunophenotypic pattern associated with CD8 T-cell pathology in HIV-2 infection, in relation to viremia and markers of disease progression. The relationships between pathological differences of the CD8 T-cell memory population and viremia were analyzed in blood samples obtained from an occupational cohort in Guinea-Bissau, including HIV-2 viremic and aviremic individuals. For comparison, samples from HIV-1- or dually HIV-1/2-infected and seronegative individuals were obtained from the same cohort. CD8 T-cell exhaustion was evaluated by the combined expression patterns of activation, stimulatory and inhibitory immune checkpoint markers analyzed using multicolor flow cytometry and advanced bioinformatics. Unsupervised multidimensional clustering analysis identified a cluster of late differentiated CD8 T-cells expressing activation (CD38+, HLA-DRint/high), co-stimulatory (CD226+/-), and immune inhibitory (2B4+, PD-1high, TIGIThigh) markers that distinguished aviremic from viremic HIV-2, and treated from untreated HIV-1-infected individuals. This CD8 T-cell population displayed close correlations to CD4%, viremia, and plasma levels of IP-10, sCD14 and beta-2 microglobulin in HIV-2 infection. Detailed analysis revealed that aviremic HIV-2-infected individuals had higher frequencies of exhausted TIGIT+ CD8 T-cell populations lacking CD226, while reduced percentage of stimulation-receptive TIGIT-CD226+ CD8 T-cells, compared to seronegative individuals. Our results suggest that HIV-2 infection, independent of viremia, skews CD8 T-cells towards exhaustion and reduced co-stimulation readiness. Further knowledge on CD8 T-cell phenotypes might provide help in therapy monitoring and identification of immunotherapy targets.

scholarly journals Highly expression of Tim-3 on HIV-specific T cells associated with disease progression and T-cell exhaustion in HIV-1 infected Chinese

Retrovirology ◽  
2012 ◽  
Vol 9 (Suppl 2) ◽  
pp. P270
Author(s):  
Z Liu ◽  
K Hong ◽  
M Jia ◽  
J Hao ◽  
Z Gao ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Disease Progression ◽  
T Cell Exhaustion ◽  
Cell Exhaustion ◽  
Hiv 1

scholarly journals Tim-3 adaptor protein Bat3 is a molecular checkpoint of T cell terminal differentiation and exhaustion

2021 ◽  
Vol 7 (18) ◽  
pp. eabd2710
Author(s):  
Chen Zhu ◽  
Karen O. Dixon ◽  
Kathleen Newcomer ◽  
Guangxiang Gu ◽  
Sheng Xiao ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Adaptor Protein ◽  
Transcriptional Analysis ◽  
T Cell Exhaustion ◽  
Cell Exhaustion ◽  
Cell Dysfunction ◽  
Autoreactive T Cell ◽  
Autoimmune Conditions ◽  
T Cell Dysfunction

T cell exhaustion has been associated with poor prognosis in persistent viral infection and cancer. Conversely, in the context of autoimmunity, T cell exhaustion has been favorably correlated with long-term clinical outcome. Understanding the development of exhaustion in autoimmune settings may provide underlying principles that can be exploited to quell autoreactive T cells. Here, we demonstrate that the adaptor molecule Bat3 acts as a molecular checkpoint of T cell exhaustion, with deficiency of Bat3 promoting a profound exhaustion phenotype, suppressing autoreactive T cell–mediated neuroinflammation. Mechanistically, Bat3 acts as a critical mTORC2 inhibitor to suppress Akt function. As a result, Bat3 deficiency leads to increased Akt activity and FoxO1 phosphorylation, indirectly promoting Prdm1 expression. Transcriptional analysis of Bat3−/− T cells revealed up-regulation of dysfunction-associated genes, concomitant with down-regulation of genes associated with T cell effector function, suggesting that absence of Bat3 can trigger T cell dysfunction even under highly proinflammatory autoimmune conditions.

scholarly journals Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254243
Author(s):  
Meritxell Llorens-Revull ◽  
Maria Isabel Costafreda ◽  
Angie Rico ◽  
Mercedes Guerrero-Murillo ◽  
Maria Eugenia Soria ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Hepatitis C ◽  
T Cell ◽  
Cd8 T Cells ◽  
Viral Clearance ◽  
Cd4 T Cell ◽  
Care Hospital ◽  
T Cell Exhaustion ◽  
Cell Exhaustion

Background & aims HCV CD4+ and CD8+ specific T cells responses are functionally impaired during chronic hepatitis C infection. DAAs therapies eradicate HCV infection in more than 95% of treated patients. However, the impact of HCV elimination on immune responses remain controversial. Here, we aimed to investigate whether HCV cure by DAAs could reverse the impaired immune response to HCV. Methods We analyzed 27 chronic HCV infected patients undergoing DAA treatment in tertiary care hospital, and we determined the phenotypical and functional changes in both HCV CD8+ and CD4+ specific T-cells before and after viral clearance. PD-1, TIM-3 and LAG-3 cell-surface expression was assessed by flow cytometry to determine CD4+ T cell exhaustion. Functional responses to HCV were analyzed by IFN-Ɣ ELISPOT, intracellular cytokine staining (IL-2 and IFN-Ɣ) and CFSE-based proliferation assays. Results We observed a significant decrease in the expression of PD-1 in CD4+ T-cells after 12 weeks of viral clearance in non-cirrhotic patients (p = 0.033) and in treatment-naive patients (p = 0.010), indicating a partial CD4 phenotype restoration. IFN-Ɣ and IL-2 cytokines production by HCV-specific CD4+ and CD8+ T cells remained impaired upon HCV eradication. Finally, a significant increase of the proliferation capacity of both HCV CD4+ and CD8+ specific T-cells was observed after HCV elimination by DAAs therapies. Conclusions Our results show that in chronically infected patients HCV elimination by DAA treatment lead to partial reversion of CD4+ T cell exhaustion. Moreover, proliferative capacity of HCV-specific CD4+ and CD8+ T cells is recovered after DAA’s therapies.

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