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

• Published in: Blood 2011-04, Vol.117 (14), p.3799-3808
• Main Authors: Hersperger, Adam R., Martin, Jeffrey N., Shin, Lucy Y., Sheth, Prameet M., Kovacs, Colin M., Cosma, Gabriela L., Makedonas, George, Pereyra, Florencia, Walker, Bruce D., Kaul, Rupert, Deeks, Steven G., Betts, Michael R.
• Format: Article
• Language: English
• Subjects: Anti-HIV Agents - therapeutic use; Antiretroviral Therapy, Highly Active; Biological and medical sciences; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - pathology; Cohort Studies; Cross-Sectional Studies; Disease Progression; Granzymes - metabolism; Hematologic and hematopoietic diseases; HIV - immunology; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - metabolism; HIV Infections - pathology; Human viral diseases; Humans; Immune Tolerance - drug effects; Immune Tolerance - immunology; Immune Tolerance - physiology; Immunobiology; Infectious diseases; Medical sciences; Perforin - metabolism; T-Box Domain Proteins - metabolism; T-Box Domain Proteins - physiology; T-Cell Antigen Receptor Specificity; Treatment Outcome; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2010-12-322727

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.