title: Increased HIV-specific CD8+ T-cell cytotoxic potential in HIV elite controllers is associated with T-bet expression.
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.
authors.affiliation: Department of Microbiology, University of Pennsylvania, 3610 Hamilton Walk, Philadelphia, PA 19104, USA.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Hersperger
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.forename: Lucy Y
authors.initials: LY
authors.lastname: Shin
authors.forename: Prameet M
authors.initials: PM
authors.lastname: Sheth
authors.forename: Colin M
authors.initials: CM
authors.lastname: Kovacs
authors.forename: Gabriela L
authors.initials: GL
authors.lastname: Cosma
authors.forename: George
authors.initials: G
authors.lastname: Makedonas
authors.forename: Florencia
authors.initials: F
authors.lastname: Pereyra
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Rupert
authors.initials: R
authors.lastname: Kaul
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: Michael R
authors.initials: MR
authors.lastname: Betts
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D053804:Granzymes / Q000378:metabolism; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D054353:Perforin / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000378:metabolism* / Q000502:physiology; D037182:T-Cell Antigen Receptor Specificity; D016896:Treatment Outcome; D000098815:T-bet Transcription Factor
chemical_list: D019380:Anti-HIV Agents; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes