γδ T-cell anergy in human immunodeficiency virus-infected persons with 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 defective response to non-peptidic antigens was observed in human immunodeficiency 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 role of highly active antiretroviral therapy (HAART) on gamma delta T-cell functions. Peripheral gamma delta T-cell distribution and in vitro reactivity 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 decrease in V delta 2 T-cell number. Moreover, IPP-stimulated V delta 2 T cells from the HIV-OIC group displayed a major defect in interferon-gamma (IFN-gamma) production. Interestingly, HAART induced a sustained recovery of naive CD45RA(+) and CD62L(+) T cells and restored gamma delta T-cell function. Accordingly, in vitro CD45RA depletion resulted in gamma delta T-cell hyporesponsiveness. Altogether, the incidence of gamma delta T-cell anergy was increased in HIV-OIC patients and dependent on CD45RA helper function. Moreover, HAART was able to restore gamma delta T-cell reactivity, extending the immune recovery to non-peptidic microbial antigens.