Mycobacteria-reactive gamma delta T cells in HIV-infected individuals: lack of V gamma 9 cell responsiveness is due to deficiency of antigen-specific CD4 T helper type 1 cells.
Human gamma delta T lymphocytes expressing the variable T cell receptor elements V gamma 9 paired with V delta 2 are activated by antigen derived from Mycobacterium tuberculosis (M. tb.) and presented by antigen-presenting cells (APC). The subsequent proliferation is strictly dependent on the presence of CD4+ TCR alpha beta+ T helper type 1 (Th1) cells producing interleukin-2 (IL-2). In this study, we report that the reactivity of V gamma 9 cells to M. tb. stimulation in vitro was drastically decreased or absent in the majority of the analyzed HIV-1-infected individuals (CDC stages III and IV). We show that the failure of V gamma 9 cells from HIV+ individuals to proliferate following M. tb. stimulation was not due to an intrinsic qualitative or quantitative defect of gamma delta T cells but rather to a deficiency of M. tb.-reactive CD4 Th1 cells. Thus, V gamma 9 responsiveness could be restored if cultures of M. tb.-stimulated T cells from HIV+ donors were reconstituted with one of the following: (i) exogenous IL-2 (ii) purified CD4 T cells from allogeneic donors; or (iii) T cell-depleted APC from allogeneic donors. In the majority of HIV+ patients, the defective Th1 activity of M. tb.-stimulated CD4 T cells could be decreased neither by cytokines known to favor Th1 development (IL-12, interferon-gamma) nor by neutralization of the Th1-suppressing Th2 cytokine IL-10. We suggest that measurement of V gamma 9 cell expansion within M. tb.-stimulated peripheral blood mononuclear cells provides a sensitive assay for the functional capacity of antigen (M. tb.)-specific CD4 Th1 cells in HIV-infected individuals.
Wesch
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Department of Immunology, Paul Ehrlich Institute, Langen, Germany.
Kabelitz
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Friese
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Pechhold
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K
D018791:CD4 Lymphocyte Count; D000939:Epitopes / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000172:deficiency; D007376:Interleukin-2 / Q000172:deficiency; D008213:Lymphocyte Activation; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
D000939:Epitopes; D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma