T-cell hyporesponsiveness induced by activated macrophages through nitric oxide production in mice infected with Mycobacterium tuberculosis

Shigeki Nabeshima, Mari Nomoto, Goro Matsuzaki, Kenji Kishihara, Hatsumi Taniguchi, Shin Ichi Yoshida, Kikuo Nomoto

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

In active tuberculosis, T-cell response to Mycobacterium tuberculosis is known to be reduced. In the course of Mycobacterium tuberculosis infection in mice, we observed that T-cell proliferation in response to M. tuberculosis purified protein derivative (PPD) reached the maximum level on day 7, then declined to the minimal level on day 14, and persisted at a low level through day 28 postinfection. The frequency of PPD-specific CD4 T cells in the spleen on day 28 decreased to one-sixth on day 7. To further investigate the mechanism of this T-cell hyporesponsiveness, we next analyzed the suppressive activity of spleen macrophages on T-cell function. The nonspecific proliferative response of naive T cells and the PPD-specific proliferative response of T cells were suppressed by day 28 macrophages, but not by day 7 macrophages or naive macrophages. This reduction of proliferative response was restored by addition of nitric oxide synthesis inhibitor, N(G)-monoethyl- L-arginine monoacetate, but not by monoclonal antibody against interleukin 10 or transforming growth factor β. These data indicate that the macrophages from mice chronically infected with M. tuberculosis suppress T-cell response through production of nitric oxide, suggesting that nitric oxide-induced elimination mediated by activated macrophages may reduce the T-cell response and the number of mycobacterium-specific CD4 T cells in vivo.

Original languageEnglish
Pages (from-to)3221-3226
Number of pages6
JournalInfection and Immunity
Volume67
Issue number7
DOIs
Publication statusPublished - 1999

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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