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 gamma delta T cells. CD4(+) and gamma delta T cells were compared for their ability to regulate IFN-gamma, TNF-alpha, 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 gamma delta T cells mere purified by negative selection and tested in response to autologous monocytes infected with M. tuberculosis. Both subsets produced equal amounts of secreted IFN-gamma. However, the precursor frequency of IFN-gamma secreting gamma delta T cells was half that of CD4(+) T cells, indicating that gamma delta T cells were more efficient producers of IFN-gamma than CD4(+) T cells. TNF-alpha production was markedly enhanced by addition of CD4(+) and gamma delta T cells to M. tuberculosis infected monocytes, and TNF-alpha was produced by both T cells and monocytes. No differences in TNF-alpha enhancement were noted between CD4(+) and gamma delta T cells. IL-10 production by M. tuberculosis infected monocytes was not modulated by CD4(+) or gamma delta T cells. Thus CD4(+) and gamma delta T cells had similar roles in differential regulation of IFN-gamma, TNF-alpha, 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-gamma production was dependent on antigen presentation and costimulators provided by monocytes. TNF-alpha levels were increased by addition of TNF-alpha produced by T cells and IL-10 production by monocytes was not modulated by CD4(+) or gamma delta T cells, (C) 1999 Academic Press.