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Infection and Immunity, July 1999, p. 3221-3226, Vol. 67, No. 7
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

T-Cell Hyporesponsiveness Induced by Activated Macrophages through Nitric Oxide Production in Mice Infected with Mycobacterium tuberculosis

Shigeki Nabeshima,1,* Mari Nomoto,1 Goro Matsuzaki,1 Kenji Kishihara,1 Hatsumi Taniguchi,2 Shin-ichi Yoshida,2,dagger and Kikuo Nomoto1

Department of Immunology, Medical Institute of Bioregulation, Kyushu University,1 and Department of Microbiology, School of Medicine, University of Occupational and Environmental Health,2 Fukuoka, Japan

Received 17 August 1998/Returned for modification 14 October 1998/Accepted 31 March 1999

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, NG-monoethyl-L-arginine monoacetate, but not by monoclonal antibody against interleukin 10 or transforming growth factor beta . 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.

* Corresponding author. Present address: Department of General Medicine, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812, Japan. Phone: 81 92 642 5909. Fax: 81 92 642 5916. E-mail: snabe{at}genmedpr.med.kyushu-u.ac.jp.

dagger Present address: Department of Virology, School of Medicine, Kyushu University, Fukuoka 812, Japan.

Infection and Immunity, July 1999, p. 3221-3226, Vol. 67, No. 7
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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