Expansion of inefficient HIV-specific CD8 T cells during acute infection

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. MichaelMerlin L. Robb, Hendrik Streeck*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

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- CD8dim T cell population, the minority populations of CD8bright T cells are significantly more effective in inhibiting HIV replication. Furthermore, the frequency of CD8dim 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 CD8dim 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 CD8dim T cell population less efficient in controlling HIV viremia.

Original languageEnglish
Pages (from-to)4005-4016
Number of pages12
JournalJournal of Virology
Volume90
Issue number8
DOIs
StatePublished - 1 Apr 2016
Externally publishedYes

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