Increased HIV-specific CD8+ T-cell Cytotoxic Potential in HIV Elite Controllers is Associated with T-bet Expression

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2011 Feb 4

PMID 21289310

Citations 112

Authors

Adam R Hersperger

Jeffrey N Martin

Lucy Y Shin

Prameet M Sheth

Colin M Kovacs

Gabriela L Cosma

George Makedonas

Florencia Pereyra

Bruce D Walker

Rupert Kaul

Steven G Deeks

Michael R Betts

Affiliations

Soon will be listed here.

Abstract

Recent data suggest that CD8+ T-cell effector activity is an important component in the control of HIV replication in elite controllers (ECs). One critical element of CD8+ T-cell effector function and differentiation is the T-box transcription factor T-bet. In the present study, we assessed T-bet expression, together with the effector proteins perforin, granzyme A (Grz A), granzyme B (Grz B), and granulysin, in HIV-specific CD8+ T cells from ECs (n = 20), chronically infected progressors (CPs; n = 18), and highly active antiretroviral therapy (HAART)-suppressed individuals (n = 19). Compared with the other cohort groups, HIV-specific CD8+ T cells among ECs demonstrated a superior ability to express perforin and Grz B, but with no detectable difference in the levels of Grz A or granulysin. We also observed higher levels of T-bet in HIV-specific CD8+ T cells from ECs, with an ensuing positive correlation between T-bet and levels of both perforin and Grz B. Moreover, HIV-specific CD8+ T cells in ECs up-regulated T-bet to a greater extent than CPs after in vitro expansion, with concomitant up-regulation of perforin and Grz B. These results suggest that T-bet may play an important role in driving effector function, and its modulation may lead to enhanced effector activity against HIV.

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