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Delayed differentiation of potent effector CD8 + T cells reducing viremia and reservoir seeding in acute HIV infection.
- Source :
-
Science translational medicine [Sci Transl Med] 2017 Feb 15; Vol. 9 (377). - Publication Year :
- 2017
-
Abstract
- CD8 <superscript>+</superscript> T cells play a critical role in controlling HIV viremia and could be important in reducing HIV-infected cells in approaches to eradicate HIV. The simian immunodeficiency virus model provided the proof of concept for a CD8 <superscript>+</superscript> T cell-mediated reservoir clearance but showed conflicting evidence on the role of these cells to eliminate HIV-infected cells. In humans, HIV-specific CD8 <superscript>+</superscript> T cell responses have not been associated with a reduction of the HIV-infected cell pool in vivo. We studied HIV-specific CD8 <superscript>+</superscript> T cells in the RV254 cohort of individuals initiating ART in the earliest stages of acute HIV infection (AHI). We showed that the HIV-specific CD8 <superscript>+</superscript> T cells generated as early as AHI stages 1 and 2 before peak viremia are delayed in expanding and acquiring effector functions but are endowed with higher memory potential. In contrast, the fully differentiated HIV-specific CD8 <superscript>+</superscript> T cells at peak viremia in AHI stage 3 were more prone to apoptosis but were associated with a steeper viral load decrease after ART initiation. Their capacity to persist in vivo after ART initiation correlated with a lower HIV DNA reservoir. These findings demonstrate that HIV-specific CD8 <superscript>+</superscript> T cell magnitude and differentiation are delayed in the earliest stages of infection. These results also demonstrate that potent HIV-specific CD8 <superscript>+</superscript> T cells contribute to the reduction of the pool of HIV-producing cells and the HIV reservoir seeding in vivo and provide the rationale to design interventions aiming at inducing these potent responses to cure HIV infection.<br /> (Copyright © 2017, American Association for the Advancement of Science.)
- Subjects :
- Acute Disease
Adult
Antiretroviral Therapy, Highly Active
Cell Proliferation
Cytokines metabolism
Female
HIV Infections drug therapy
HIV Infections pathology
Humans
Male
Survival Analysis
Viral Load
Viremia virology
CD8-Positive T-Lymphocytes immunology
Cell Differentiation
Disease Reservoirs virology
HIV Infections immunology
HIV Infections virology
Viremia immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1946-6242
- Volume :
- 9
- Issue :
- 377
- Database :
- MEDLINE
- Journal :
- Science translational medicine
- Publication Type :
- Academic Journal
- Accession number :
- 28202771
- Full Text :
- https://doi.org/10.1126/scitranslmed.aag1809