Increased HIV-specific CD8+ T-cell cytotoxic potential in HIV elite controllers is associated with T-bet expression

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 anti-retroviral 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. (Blood. 2011;117(14):3799-3808)