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Overexpression of CD6 and PD-1 Identifies Dysfunctional CD8+ T-Cells During Chronic SIV Infection of Rhesus Macaques.


ABSTRACT: Effective CD8+ T-cell responses play an important role in determining the course of SIV/HIV viral infection. Here we identified a unique population of dysfunctional CD8+ T-cells in lymphoid tissues and bronchoalveolar lavage (BAL) of rhesus macaques with chronic SIV infection characterized by co-expression of CD6 and PD-1. The frequency of CD6 and PD-1 co-expressing CD8+ T-cells was significantly increased in lymphoid tissues and BAL during chronic SIV infection compared to pre-infection levels. These CD6+PD-1+CD8+ T-cells displayed impaired proliferation, cytokine secretion and cytotoxicity compared to their CD6-PD-1+CD8+ T cell counterparts. The frequency of CD8+PD-1+ and CD8+CD6-PD-1+ T-cells in the lymph node and bone marrow did not correlate with SIV viral load, whereas the frequency of CD8+CD6+PD-1+ T-cells positively correlated with SIV viral load in these tissues highlighting the contribution of CD6 to disease progression. CD6+PD-1+CD8+ T-cells expressed elevated levels of SHP2 phosphatase compared to CD6-PD-1+CD8+ T-cells providing a potential mechanism by which CD6 may induce T-cell dysfunction during chronic SIV infection. Combined targeting of CD6 and PD-1 effectively revived the CD8+ T-cell proliferative response in vitro suggesting a strategy for potential therapeutic benefit.

SUBMITTER: Enyindah-Asonye G 

PROVIDER: S-EPMC6961594 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Overexpression of CD6 and PD-1 Identifies Dysfunctional CD8<sup>+</sup> T-Cells During Chronic SIV Infection of Rhesus Macaques.

Enyindah-Asonye Gospel G   Nwankwo Anthony A   Rahman Mohammad Arif MA   Hunegnaw Ruth R   Hogge Christopher C   Helmold Hait Sabrina S   Ko Eun-Ju EJ   Hoang Tanya T   Robert-Guroff Marjorie M  

Frontiers in immunology 20200108


Effective CD8<sup>+</sup> T-cell responses play an important role in determining the course of SIV/HIV viral infection. Here we identified a unique population of dysfunctional CD8<sup>+</sup> T-cells in lymphoid tissues and bronchoalveolar lavage (BAL) of rhesus macaques with chronic SIV infection characterized by co-expression of CD6 and PD-1. The frequency of CD6 and PD-1 co-expressing CD8<sup>+</sup> T-cells was significantly increased in lymphoid tissues and BAL during chronic SIV infection  ...[more]

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