γδ T‐cell anergy in human immunodeficiency virus‐infected persons with opportunistic infections and recovery after highly active antiretroviral therapy

• Published in: Immunology 2000-08, Vol.100 (4), p.481-486
• Main Authors: Martini, F., Urso, R., Gioia, C., De Felici, A., Narciso, P., Amendola, A., Paglia, M. G., Colizzi, V., Poccia, F.
• Format: Article
• Language: English
• Subjects: Original
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1046/j.1365-2567.2000.00068.x

Summary 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.