Regulation by cytokines (IL-12, IL-15, IL-4 and IL-10) of the Vgamma9Vdelta2 T cell response to mycobacterial phosphoantigens in responder and anergic HIV-infected persons

• Published in: European journal of immunology 1999-01, Vol.29 (1), p.90-99
• Main Authors: Boullier, S, Poquet, Y, Debord, T, Fournie, J J, Gougeon, M L
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Antigens, Bacterial - administration & dosage; Case-Control Studies; HIV Infections - immunology; Humans; Immune Tolerance; In Vitro Techniques; Interferon-gamma - biosynthesis; Interleukin-10 - pharmacology; Interleukin-12 - pharmacology; Interleukin-15 - pharmacology; Interleukin-4 - biosynthesis; Interleukin-4 - pharmacology; Interleukins - pharmacology; Lymphocyte Activation; Mycobacterium - immunology; Receptors, Antigen, T-Cell, gamma-delta - metabolism; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; Th1 Cells - drug effects; Th1 Cells - immunology; Th2 Cells - drug effects; Th2 Cells - immunology; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 0014-2980

Human Vgamma9Vdelta2 T cells contribute to immunity against intracellular pathogens and recognize nonpeptidic antigens, such as the mycobacterial phosphoantigen TUBAg. HIV infection is associated with a polyclonal decrease of peripheral Vgamma9Vdelta2 T cells and we previously reported that the remaining cells show a proliferative anergy to stimulation with Mycobacterium tuberculosis in 60% of patients. Because of alterations in the Th1/Th2 cytokine balance reported in HIV infection, we analyzed, at the single-cell level, the influence of exogenous IL-4, IL-10, IL-12 and IL-15 on the response to mycobacterial phosphoantigens of gammadelta T cells from HIV-infected patients and healthy donors. We report that the strong gammadelta T cell response to TUBAg is characterized by the rapid and selective production of the Th1/proinflammatory cytokines IFN-gamma and TNF-alpha in responder HIV-infected donors. In addition, a positive regulation by IL-12 and IL-15 of the production of these cytokines by Vgamma9Vdelta2 T cells in response to nonpeptidic ligands was observed, whereas IL-4 and IL-10 had no effect. In contrast, Vgamma9Vdelta2 T cells from the anergic HIV-infected donors had lost the ability to produce Th1 cytokines and were not shifted towards a Th2 profile. Furthermore, neither IL-12 nor IL-15 could reverse this functional anergy. The consequences of these observations are discussed in the context of HIV pathogenesis.