T cell-derived IL-10 antagonizes macrophage function in mycobacterial infection.
Pathogenic mycobacteria survive within macrophages despite T cell responses that activate host defenses against most pathogens. Among cytokines produced by T cells, IL-10 is known to negatively regulate Th1 cells as well as macrophages. IL-10 has been shown to inhibit the anti-mycobacterial activity of macrophages in vitro and could account for the ability of mycobacteria to survive intracellularly. To test the inhibitory functions of IL-10 in vivo, transgenic mice that secrete IL-10 from the T cell compartment were constructed and infected with Calmette-Guérin bacillus (Mycobacterium bovis). These mice were unable to clear the infection and developed large bacterial burdens. Nonetheless, their T cells produced abundant amounts of IFN-gamma and IL-2 in response to Ag challenge. These results indicate that the presence of excess IL-10 had little, if any, effect on T cell function or development during the immune response to Calmette-Guérin bacillus. Rather, the data suggest that IL-10 helps maintain mycobacterial infections by acting primarily at the level of the macrophage, overriding anti-mycobacterial signals delivered by IFN-gamma.
Murray
P J
PJ
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Wang
L
L
Onufryk
C
C
Tepper
R I
RI
Young
R A
RA
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D009163:Mycobacterium bovis / Q000187:drug effects* / Q000276:immunology* / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics*; D014376:Tuberculosis / Q000188:drug therapy / Q000276:immunology
D007376:Interleukin-2; D016753:Interleukin-10; D007371:Interferon-gamma