Temporal Dynamics of CD8+ T Cell Effector Responses during Primary HIV Infection.
Journal Article (Clinical Trial;Journal Article;Multicenter Study)
The loss of HIV-specific CD8+ T cell cytolytic function is a primary factor underlying progressive HIV infection, but whether HIV-specific CD8+ T cells initially possess cytolytic effector capacity, and when and why this may be lost during infection, is unclear. Here, we assessed CD8+ T cell functional evolution from primary to chronic HIV infection. We observed a profound expansion of perforin+ CD8+ T cells immediately following HIV infection that quickly waned after acute viremia resolution. Selective expression of the effector-associated transcription factors T-bet and eomesodermin in cytokine-producing HIV-specific CD8+ T cells differentiated HIV-specific from bulk memory CD8+ T cell effector expansion. As infection progressed expression of perforin was maintained in HIV-specific CD8+ T cells with high levels of T-bet, but not necessarily in the population of T-betLo HIV-specific CD8+ T cells that expand as infection progresses. Together, these data demonstrate that while HIV-specific CD8+ T cells in acute HIV infection initially possess cytolytic potential, progressive transcriptional dysregulation leads to the reduced CD8+ T cell perforin expression characteristic of chronic HIV infection.
Full Text
Duke Authors
Cited Authors
- Demers, KR; Makedonas, G; Buggert, M; Eller, MA; Ratcliffe, SJ; Goonetilleke, N; Li, CK; Eller, LA; Rono, K; Maganga, L; Nitayaphan, S; Kibuuka, H; Routy, J-P; Slifka, MK; Haynes, BF; McMichael, AJ; Bernard, NF; Robb, ML; Betts, MR
Published Date
- August 2016
Published In
Volume / Issue
- 12 / 8
Start / End Page
- e1005805 -
PubMed ID
- 27486665
Pubmed Central ID
- PMC4972399
Electronic International Standard Serial Number (EISSN)
- 1553-7374
Digital Object Identifier (DOI)
- 10.1371/journal.ppat.1005805
Language
- eng
Conference Location
- United States