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

Autor:	Enyindah-Asonye G; Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States., Nwankwo A; Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States., Rahman MA; Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States., Hunegnaw R; Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States., Hogge C; Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States., Helmold Hait S; Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States., Ko EJ; Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States., Hoang T; Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States., Robert-Guroff M; Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2020 Jan 08; Vol. 10, pp. 3005. Date of Electronic Publication: 2020 Jan 08 (Print Publication: 2019).
DOI:	10.3389/fimmu.2019.03005
Abstrakt:	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. (Copyright © 2020 Enyindah-Asonye, Nwankwo, Rahman, Hunegnaw, Hogge, Helmold Hait, Ko, Hoang and Robert-Guroff.)
Databáze:	MEDLINE
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