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J Virol. 2016 Mar 28;90(8):4005-4016. doi: 10.1128/JVI.02785-15. Print 2016 Apr.

Expansion of Inefficient HIV-Specific CD8 T Cells during Acute Infection.

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U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
Department of Immunology & Microbiology, University of North Carolina, Chapel Hill, North Carolina, USA.
Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Retrovirology, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences (USAMC-AFRIMS), Bangkok, Thailand.
Walter Reed Project-Kenya, Kericho, Kenya.
Walter Reed Program-Tanzania, Mbeya, Tanzania.
Makerere University Walter Reed Project, Kampala, Uganda.
International Vaccine Institute, Seoul, South Korea.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
Institute for HIV Research, University Hospital in Essen, University of Duisburg-Essen, Essen, Germany.


Attrition within the CD4(+)T cell compartment, high viremia, and a cytokine storm characterize the early days after HIV infection. When the first emerging HIV-specific CD8(+)T cell responses gain control over viral replication it is incomplete, and clearance of HIV infection is not achieved even in the rare cases of individuals who spontaneously control viral replication to nearly immeasurably low levels. Thus, despite their partial ability to control viremia, HIV-specific CD8(+)T cell responses are insufficient to clear HIV infection. Studying individuals in the first few days of acute HIV infection, we detected the emergence of a unique population of CD38(+)CD27(-)CD8(+)T cells characterized by the low expression of the CD8 receptor (CD8(dim)). Interestingly, while high frequencies of HIV-specific CD8(+)T cell responses occur within the CD38(+)CD27(-)CD8(dim)T cell population, the minority populations of CD8(bright)T cells are significantly more effective in inhibiting HIV replication. Furthermore, the frequency of CD8(dim)T cells directly correlates with viral load and clinical predictors of more rapid disease progression. We found that a canonical burst of proliferative cytokines coincides with the emergence of CD8(dim)T cells, and the size of this population inversely correlates with the acute loss of CD4(+)T cells. These data indicate, for the first time, that early CD4(+)T cell loss coincides with the expansion of a functionally impaired HIV-specific CD8(dim)T cell population less efficient in controlling HIV viremia.


A distinct population of activated CD8(+)T cells appears during acute HIV infection with diminished capacity to inhibit HIV replication and is predictive of viral set point, offering the first immunologic evidence of CD8(+)T cell dysfunction during acute infection.

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