T-Cell hyporesponsiveness induced by activated macrophages through nitric oxide production in mice infected with Mycobacterium tuberculosis.
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.
Nabeshima
S
S
Department of Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan. snabe@genmedpr.med.kyushu-u.ac.jp
Nomoto
M
M
Matsuzaki
G
G
Kishihara
K
K
Taniguchi
H
H
Yoshida
S
S
Nomoto
K
K
D000818:Animals; D005260:Female; D008213:Lymphocyte Activation / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D014376:Tuberculosis / Q000276:immunology*
D009569:Nitric Oxide