IL-10-producing T cells suppress immune responses in anergic tuberculosis patients

The lethality of Mycobacterium tuberculosis remains the highest among infec tious organisms and is linked to inadequate immune response of the host. Co ntainment and cure of tuberculosis requires an effective cell-mediated immu ne response, and the absence, during active tuberculosis infection, of dela yed-type hypersensitivity (DTH) responses to mycobacterial antigens, define d as anergy, is associated with poor clinical outcome. To investigate the b iochemical events associated with this anergy, we screened 206 patients wit h pulmonary tuberculosis and identified anergic patients by their lack of d ermal reactivity to tuberculin purified protein derivative (PPD). In vitro stimulation of T cells with PPD induced production of IL-10, IFN-gamma, and proliferation in PPD+ patients, whereas cells from anergic patients produc ed IL-10 but not IFN-gamma and failed to proliferate in response to this tr eatment. Moreover, in anergic patients IL-10-producing T cells were constit utively present, and T-cell receptor-mediated (TCR-mediated) stimulation re sulted in defective phosphorylation of TCR zeta and defective activation of ZAP-70 and MAPK. These results show that T-cell anergy can be induced by a ntigen in vivo in the intact human host and provide new insights into mecha nisms by which M, tuberculosis escapes immune surveillance.