γδ 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 γδ 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 γδ T-cell functions. Peripheral γδ T-cell distribution and in vitro reactivity to a non-peptidic mycobacterial antigen, isopentenyl pyrophosphate (IPP), were analysed. γδ T-cell subset distribution was altered more in HIV-OIC patients than in asymptomatic HIV+ subjects (HIV-ASY). Specifically, the Vδ2/Vδ1 ratio was inverted as a consequence of a decrease in Vδ2 T-cell number. Moreover, IPP-stimulated Vδ2 T cells from the HIV-OIC group displayed a major defect in interferon-γ (IFN-γ) production. Interestingly, HAART induced a sustained recovery of naive CD45RA+ and CD62L+ T cells and restored γδ T-cell function. Accordingly, in vitro CD45RA depletion resulted in γδ T-cell hyporesponsiveness. Altogether, the incidence of γδ T-cell anergy was increased in HIV-OIC patients and dependent on CD45RA helper function. Moreover, HAART was able to restore γδ T-cell reactivity, extending the immune recovery to non-peptidic microbial antigens.
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