Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Aging (Upcoming)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • Gut-Brain Axis (Jul 2021)
    • Tumor Microenvironment (Mar 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
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.
View: Text | PDF
Article

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

  • Text
  • PDF
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

×

Figure 1

Options: View larger image (or click on image) Download as PowerPoint
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.

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts