gamma delta 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: CD45RA antigen; highly active antiretroviral therapy; Human immunodeficiency virus
• ISSN: 0019-2805
• DOI: 10.1046/j.1365-2567.2000.00068.x

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 super(+)) persons, the aims of this study were twofold: to analyse the incidence of gamma delta T-cell anergy in HIV super(+) 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 super(+) 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 super(+) and CD62L super(+) 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.