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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

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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 4

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Anti–IL-10 neutralizing mAb increases proliferation of T cells from aner...
Anti–IL-10 neutralizing mAb increases proliferation of T cells from anergic TB patients in response to PPD, alloantigen, and PMA plus PHA. CD4+ T cells from two anergic patients (AP3 and AP5) were stimulated with PPD, allogeneic PBMCs, or PMA plus PHA in the presence of either media, neutralizing anti–IL-10 mAb, or isotype-matched control antibody. After the indicated time intervals of culture as described in Methods, response was determined by 3H-thymidine incorporation.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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