Regulation of Human CD4 + αβ T-Cell-Receptor-Positive (TCR + ) and γδ TCR + T-Cell Responses to Mycobacterium tuberculosis by Interleukin-10 and Transforming Growth Factor β

Mycobacterium tuberculosis is the etiologic agent of human tuberculosis and is estimated to infect one-third of the world's population. Control of M. tuberculosis requires T cells and macrophages. T-cell function is modulated by the cytokine environment, which in mycobacterial infection is a balance of proinflammatory (interleukin-1 [IL-1], IL-6, IL-8, IL-12, and tumor necrosis factor alpha) and inhibitory (IL-10 and transforming growth factor β [TGF-β]) cytokines. IL-10 and TGF-β are produced by M. tuberculosis -infected macrophages. The effect of IL-10 and TGF-β on M. tuberculosis -reactive human CD4 + and γδ T cells, the two major human T-cell subsets activated by M. tuberculosis , was investigated. Both IL-10 and TGF-β inhibited proliferation and gamma interferon production by CD4 + and γδ T cells. IL-10 was a more potent inhibitor than TGF-β for both T-cell subsets. Combinations of IL-10 and TGF-β did not result in additive or synergistic inhibition. IL-10 inhibited γδ and CD4 + T cells directly and inhibited monocyte antigen-presenting cell (APC) function for CD4 + T cells and, to a lesser extent, for γδ T cells. TGF-β inhibited both CD4 + and γδ T cells directly and had little effect on APC function for γδ and CD4 + T cells. IL-10 down-regulated major histocompatibility complex (MHC) class I, MHC class II, CD40, B7-1, and B7-2 expression on M. tuberculosis -infected monocytes to a greater extent than TGF-β. Neither cytokine affected the uptake of M. tuberculosis by monocytes. Thus, IL-10 and TGF-β both inhibited CD4 + and γδ T cells but differed in the mechanism used to inhibit T-cell responses to M. tuberculosis .