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Title: Expansion of inefficient HIV-specific CD8 T cells during acute infection
Authors: Michael A. Eller
Nilu Goonetilleke
Boonrat Tassaneetrithep
Leigh Anne Eller
Margaret C. Costanzo
Susan Johnson
Michael R. Betts
Shelly J. Krebs
Bonnie M. Slike
Sorachai Nitayaphan
Kathleen Rono
Sodsai Tovanabutra
Lucas Maganga
Hannah Kibuuka
Linda Jagodzinski
Sheila Peel
Morgane Rolland
Mary A. Marovich
Jerome H. Kim
Nelson L. Michael
Merlin L. Robb
Hendrik Streeck
Walter Reed Army Institute of Research
The University of North Carolina at Chapel Hill
Mahidol University
University of Pennsylvania
Armed Forces Research Institute of Medical Sciences, Thailand
Walter Reed Project-Kenya
Walter Reed Program-Tanzania
Makerere University
Universitats Klinikum Essen und Medizinische Fakultat
International Vaccine Institute, Seoul
National Institute of Allergy and Infectious Diseases
Keywords: Agricultural and Biological Sciences;Immunology and Microbiology
Issue Date: 1-Apr-2016
Citation: Journal of Virology. Vol.90, No.8 (2016), 4005-4016
Abstract: © 2016, American Society for Microbiology. 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 (CD8dim). Interestingly, while high frequencies of HIV-specific CD8+T cell responses occur within the CD38+CD27-CD8dimT cell population, the minority populations of CD8brightT cells are significantly more effective in inhibiting HIV replication. Furthermore, the frequency of CD8dimT 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 CD8dimT 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 CD8dimT cell population less efficient in controlling HIV viremia.
ISSN: 10985514
Appears in Collections:Scopus 2016-2017

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