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Immunity. 2015 Sep 15;43(3):591-604. doi: 10.1016/j.immuni.2015.08.012. Epub 2015 Sep 8.

Magnitude and Kinetics of CD8+ T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point.

Author information

1
HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
2
HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa.
3
KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa; Department of Immunology and Microbiology, University of Copenhagen, 2200-Copenhagen N, Denmark.
4
KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa.
5
Department of Chemical Engineering, Massachusetts Institute of Technology, 25 Ames St, Cambridge, MA 02142, USA.
6
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
7
Department of Paediatrics, University of Oxford, Oxford OX1 3SY, United Kingdom.
8
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA; KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa.
9
HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa; Department of Paediatrics, University of Oxford, Oxford OX1 3SY, United Kingdom.
10
Department of Immunology and Microbiology, University of Copenhagen, 2200-Copenhagen N, Denmark.
11
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, 25 Ames St, Cambridge, MA 02142, USA.
12
HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA; KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa; Max Planck Institute for Infection Biology, Chariteplatz 1, 10117, Berlin, Germany.
13
HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: bwalker@mgh.harvard.edu.

Abstract

CD8(+) T cells contribute to the control of HIV, but it is not clear whether initial immune responses modulate the viral set point. We screened high-risk uninfected women twice a week for plasma HIV RNA and identified 12 hyperacute infections. Onset of viremia elicited a massive HIV-specific CD8(+) T cell response, with limited bystander activation of non-HIV memory CD8(+) T cells. HIV-specific CD8(+) T cells secreted little interferon-γ, underwent rapid apoptosis, and failed to upregulate the interleukin-7 receptor, known to be important for T cell survival. The rapidity to peak CD8(+) T cell activation and the absolute magnitude of activation induced by the exponential rise in viremia were inversely correlated with set point viremia. These data indicate that rapid, high magnitude HIV-induced CD8(+) T cell responses are crucial for subsequent immune control of acute infection, which has important implications for HIV vaccine design.

PMID:
26362266
PMCID:
PMC4575777
DOI:
10.1016/j.immuni.2015.08.012
[Indexed for MEDLINE]
Free PMC Article

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