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 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.

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

Abstract 67: Paralleled convergence of antigen load, disease progression and systemic T cell exhaustion in lung cancer and HIV-1 infection

2021 ◽  
Author(s):  
James L. Reading ◽  
Rachel Rosenthal ◽  
Lucas Black ◽  
Seng Kuong Ung ◽  
Claire Streatfield ◽  
...  
Keyword(s):  
Lung Cancer ◽  
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.

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