gamma delta T-cell anergy in human immunodeficiency virus-infected personswith opportunistic infections and recovery after highly active antiretroviral therapy

gamma delta T lymphocytes recognize non-peptidic microbial antigens without antigen processing and major histocompatibility complex (MHC) restriction, representing an early defence mechanism against invading pathogens. As a d efective response to non-peptidic antigens was observed in human immunodefi ciency virus-positive (HIV+) persons, the aims of this study were twofold: to analyse the incidence of gamma delta T-cell anergy in HIV+ patients with opportunistic infections/co-infections (HIV-OIC), and to investigate the r ole of highly active antiretroviral therapy (HAART) on gamma delta T-cell f unctions. Peripheral gamma delta T-cell distribution and in vitro reactivit y to a non-peptidic mycobacterial antigen, isopentenyl pyrophosphate (IPP), were analysed, gamma delta T-cell subset distribution was altered more in HIV-OIC patients than in asymptomatic HIV+ subjects (HIV-ASY). Specifically , the V delta 2/ V delta 1 ratio was inverted as a consequence of a decreas e in V delta 2 T-cell number. Moreover, IPP-stimulated V delta 2 T cells fr om the HIV-OIC group displayed a major defect in interferon-gamma (IFN-gamm a) production. Interestingly, HAART induced a sustained recovery of naive C D45RA(+) and CD62L(+) T cells and restored gamma delta T-cell function. Acc ordingly, in vitro CD45RA depletion resulted in gamma delta T-cell hyporesp onsiveness. Altogether, the incidence of gamma delta T-cell anergy was incr eased in HIV-OIC patients and dependent on CD45RA helper function. Moreover , HAART was able to restore gamma delta T-cell reactivity, extending the im mune recovery to non-peptidic microbial antigens.