Differential Regulation of IFN-γ, TNF-α, and IL-10 Production by CD4+ αβTCR+ T Cells and Vδ2+ γδ T Cells in Response to Monocytes Infected with Mycobacterium tuberculosis-H37Ra

Mycobacterium tuberculosis bacilli readily activate CD4+ and γδ T cells. CD4+ and γδ T cells were compared for their ability to regulate IFN-γ, TNF-α, and IL-10 production, cytokines with significant roles in the immune response to M. tuberculosis. PBMC from healthy tuberculin positive donors were stimulated with live M. tuberculosis-H37Ra. CD4+ and γδ T cells were purified by negative selection and tested in response to autologous monocytes infected with M. tuberculosis. Both subsets produced equal amounts of secreted IFN-γ. However, the precursor frequency of IFN-γ secreting γδ T cells was half that of CD4+ T cells, indicating that γδ T cells were more efficient producers of IFN-γ than CD4+ T cells. TNF-α production was markedly enhanced by addition of CD4+ and γδ T cells to M. tuberculosis infected monocytes, and TNF-α was produced by both T cells and monocytes. No differences in TNF-α enhancement were noted between CD4+ and γδ T cells. IL-10 production by M. tuberculosis infected monocytes was not modulated by CD4+ or γδ T cells. Thus CD4+ and γδ T cells had similar roles in differential regulation of IFN-γ, TNF-α, and IL-10 secretion in response to M. tuberculosis infected monocytes. However, the interaction between T cells and infected monocytes differed for each cytokine. IFN-γ production was dependent on antigen presentation and costimulators provided by monocytes. TNF-α levels were increased by addition of TNF-α produced by T cells and IL-10 production by monocytes was not modulated by CD4+ or γδ T cells.