HIV immune activation drives increased Eomes expression in memory CD8 T cells in association with transcriptional downregulation of CD127.

ABSTRACT: BACKGROUND:During HIV infection distinct mechanisms drive immune activation of the CD4 and CD8 T cells leading to CD4 T-cell depletion and expansion of the CD8 T-cell pool. This immune activation is polyclonal and extends beyond HIV-specific T cells. One consequence of this immune activation is a profound decrease in IL-7R? (CD127) expression on memory CD8 T cells. The mechanisms leading to this are unknown and because of the potential impact of reduced IL-7 signaling in memory T cells specific to HIV and other pathogens, in the present study we examined the molecular mechanisms implicated in this downregulation of CD127. METHODS:Membrane bound (mIL7RA) and soluble (sIL7RA) mRNA expression was determined by qRT-PCR. CD127, Eomesodermin (Eomes) and T-bet expression in healthy controls and HIV-infected patients were studied by flow cytometry. RESULTS:CD127 downregulation occurs at the transcriptional level for both mIL7RA and sIL7RA alternative spliced forms in the CD127 memory CD8 T cells. CD127 memory CD8 T cells exhibited increased Eomes expression and an 'effector-like' gene profile. These changes were associated with higher HIV-RNA levels. Following combination antiretroviral therapy (cART), there was an increase in CD127 expression over an extended period of time (>5 months) which was associated with decreased Eomes expression. CONCLUSION:CD127 is downregulated at a transcriptional level in memory CD8 T cells in association with upregulation of Eomes expression.

SUBMITTER: Hasley RB 

PROVIDER: S-EPMC7577351 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature