gammadelta T-cell anergy in human immunodeficiency virus-infected persons with opportunistic infections and recovery after highly active antiretroviral therapy.
gammadelta 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 gammadelta T-cell anergy in HIV+ positive patients with opportunistic infections/co-infections (HIV-OIC), and to investigate the role of highly active antiretroviral therapy (HAART) on gammadelta T-cell functions. Peripheral gammadelta T-cell distribution and in vitro reactivity to a non-peptidic mycobacterial antigen, isopentenyl pyrophosphate (IPP), were analysed. gammadelta T-cell subset distribution was altered more in HIV-OIC patients than in asymptomatic HIV+ subjects (HIV-ASY). Specifically, the Vdelta2/Vdelta1 ratio was inverted as a consequence of a decrease in Vdelta2 T-cell number. Moreover, IPP-stimulated Vdelta2 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 gammadelta T-cell function. Accordingly, in vitro CD45RA depletion resulted in gammadelta T-cell hyporesponsiveness. Altogether, the incidence of gammadelta T-cell anergy was increased in HIV-OIC patients and dependent on CD45RA helper function. Moreover, HAART was able to restore gammadelta T-cell reactivity, extending the immune recovery to non-peptide microbial antigens.
International Centre for AIDS & Emerging Infections, Laboratory of Clinical Pathology and 4th Clinical Division of the Institute for Infectious Diseases 'L. Spallanzoni', Rome, Italy.
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Martini
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Urso
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Gioia
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De Felici
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Narciso
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Amendola
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Paglia
V
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Colizzi
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Poccia
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000276:immunology*; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000942:Antigens, Bacterial / Q000276:immunology; D018929:Cell Culture Techniques; D017635:Clonal Anergy / Q000187:drug effects*; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D009161:Mycobacterium / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D019380:Anti-HIV Agents; D000942:Antigens, Bacterial; D016207:Cytokines; D016692:Receptors, Antigen, T-Cell, gamma-delta