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Expansion of Inefficient HIV-Specific CD8 T Cells during Acute Infection.
- Source :
-
Journal of virology [J Virol] 2016 Mar 28; Vol. 90 (8), pp. 4005-4016. Date of Electronic Publication: 2016 Mar 28 (Print Publication: 2016). - Publication Year :
- 2016
-
Abstract
- Unlabelled: 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.<br />Importance: 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.<br /> (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)
- Subjects :
- Acute Disease
Adolescent
Adult
CD4-Positive T-Lymphocytes immunology
Cell Proliferation
Epitopes
Female
HIV Infections virology
Humans
Immunophenotyping
Lymphocyte Count
Male
Middle Aged
T-Lymphocyte Subsets immunology
Viral Load
Virus Replication
Young Adult
CD8-Positive T-Lymphocytes immunology
HIV Infections immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5514
- Volume :
- 90
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 26842474
- Full Text :
- https://doi.org/10.1128/JVI.02785-15