CD8 memory T-cell differentiation during HIV infection: the role of RUNX3, Eomes, and T-bet transcription factors and their impact on CD127 expression

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NIAID	INFECTDIS-3

Authors

• R Hasley
• C Hong
• T Friesen
• C Wilhelm
• Y Nakamura
• G Kim
• J Park
• M Sneller
• G Roby
• C Rehm
• C Lane
• M Catalfamo

Abstract

Immune activation plays an important role in HIV pathogenesis, and differentially affects CD4 and CD8 T cell pools. While there is a depletion of CD4 T cells, there is an expansion of CD8 T cells, specifically with a memory-like phenotype and CD127low expression. Survival of memory CD8 T cells is dependent on IL-7 signaling, therefore we hypothesized that in the context of HIV infection, memory CD8 T cells may not be able to undergo homeostatic proliferation and their survival and development is impaired due to the loss of CD127. In the present work, we studied the T-box transcription factors T-bet and Eomes, which govern the differentiation of effector versus memory CD8 T cells respectively, and the dynamics of CD127 and RUNX3 during HIV infection. We found that the inflammatory environment maintained by HIV-RNA levels favors expression of T-bet and Eomes concomitant to CD127 repression (R=-0.7194, p<0.0001). In patients with viral loads >50 copies/ml, memory CD8 T cells were CD127lowEomes+T-bethigh; however, in treated patients, T-bet expression decreased, and memory CD8 T cells were CD127highEomes+T-betlow. These data provide new evidence for the development of long-lived memory CD8 T cells in the context of chronic HIV infection and its importance in vaccine development.

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