1. HLA class II-Restricted CD8+ T cells in HIV-1 Virus Controllers.
- Author
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Nyanhete TE, Frisbee AL, Bradley T, Faison WJ, Robins E, Payne T, Freel SA, Sawant S, Weinhold KJ, Wiehe K, Haynes BF, Ferrari G, Li QJ, Moody MA, and Tomaras GD
- Subjects
- Adult, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Female, HIV Infections virology, HIV Seropositivity, HIV-1 immunology, HIV-1 metabolism, HLA-DQ beta-Chains metabolism, HLA-DRB1 Chains metabolism, Histocompatibility Antigens Class II immunology, Histocompatibility Antigens Class II metabolism, Humans, Male, Viral Load, Virus Replication, HIV Infections immunology, HLA-DQ beta-Chains immunology, HLA-DRB1 Chains immunology
- Abstract
A paradigm shifting study demonstrated that induction of MHC class E and II-restricted CD8+ T cells was associated with the clearance of SIV infection in rhesus macaques. Another recent study highlighted the presence of HIV-1-specific class II-restricted CD8+ T cells in HIV-1 patients who naturally control infection (virus controllers; VCs). However, questions regarding class II-restricted CD8+ T cells ontogeny, distribution across different HIV-1 disease states and their role in viral control remain unclear. In this study, we investigated the distribution and anti-viral properties of HLA-DRB1*0701 and DQB1*0501 class II-restricted CD8+ T cells in different HIV-1 patient cohorts; and whether class II-restricted CD8+ T cells represent a unique T cell subset. We show that memory class II-restricted CD8+ T cell responses were more often detectable in VCs than in chronically infected patients, but not in healthy seronegative donors. We also demonstrate that VC CD8+ T cells inhibit virus replication in both a class I- and class II-dependent manner, and that in two VC patients the class II-restricted CD8+ T cells with an anti-viral gene signature expressed both CD4+ and CD8+ T cell lineage-specific genes. These data demonstrated that anti-viral memory class II-restricted CD8+ T cells with hybrid CD4+ and CD8+ features are present during natural HIV-1 infection.
- Published
- 2019
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