IL-10–producing T cells suppress immune responses in anergic tuberculosis patients
Vassiliki A. Boussiotis, … , Jean-Marc Reynes, Anne E. Goldfeld
Vassiliki A. Boussiotis, … , Jean-Marc Reynes, Anne E. Goldfeld
Published May 1, 2000
Citation Information: J Clin Invest. 2000;105(9):1317-1325. https://doi.org/10.1172/JCI9918.
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Article

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

Abstract

The lethality of Mycobacterium tuberculosis remains the highest among infectious organisms and is linked to inadequate immune response of the host. Containment and cure of tuberculosis requires an effective cell-mediated immune response, and the absence, during active tuberculosis infection, of delayed-type hypersensitivity (DTH) responses to mycobacterial antigens, defined as anergy, is associated with poor clinical outcome. To investigate the biochemical events associated with this anergy, we screened 206 patients with pulmonary tuberculosis and identified anergic patients by their lack of dermal reactivity to tuberculin purified protein derivative (PPD). In vitro stimulation of T cells with PPD induced production of IL-10, IFN-γ, and proliferation in PPD+ patients, whereas cells from anergic patients produced IL-10 but not IFN-γ and failed to proliferate in response to this treatment. Moreover, in anergic patients IL-10–producing T cells were constitutively present, and T-cell receptor–mediated (TCR-mediated) stimulation resulted in defective phosphorylation of TCRζ and defective activation of ZAP-70 and MAPK. These results show that T-cell anergy can be induced by antigen in vivo in the intact human host and provide new insights into mechanisms by which M. tuberculosis escapes immune surveillance.

Authors

Vassiliki A. Boussiotis, Eunice Y. Tsai, Edmond J. Yunis, Sok Thim, Julio C. Delgado, Christopher C. Dascher, Alla Berezovskaya, Dominique Rousset, Jean-Marc Reynes, Anne E. Goldfeld

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Figure 1

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APC from anergic TB patients do not generate a PPD-specific proliferativ...
APC from anergic TB patients do not generate a PPD-specific proliferative response of autologous T cells but can efficiently generate allo-MLR. (a) CD4+ T cells from PPD+ (responding) patients (RP) and anergic patients (AP) were stimulated with autologous APC loaded with PPD, and 3H-thymidine incorporation was determined. Results of four representative patients among 10 studied in each group are shown. (b) T cells from the same healthy volunteer donor were stimulated with APC from RP, AP, and healthy control individuals (Ctl) for 7 days, and DNA synthesis was determined by 3H-thymidine incorporation. Results of three representative individuals among eight studied in each group are shown. T cells from anergic TB patients have diminished responses to alloantigen and nonspecific mitogens. (c) CD4+ T cells from anergic and PPD+ patients were used as responders, and APC from the same healthy volunteer donor were used as stimulators. Cultures were continued for 7 days and response was assessed by 3H-thymidine incorporation. (d) CD4+ T cells from TB patients were cultured with PMA and PHA and response was examined by 3H-thimindine incorporation. Results of four representative patients among eight studied in each group are shown in c and d.