The role of interleukin-12 in acquired immunity to Mycobacterium tuberculosis infection.
The early phase of acquired cellular immunity to Mycobacterium tuberculosis infection is mediated by the emergence of protective CD4 T lymphocytes that secrete cytokines including interferon-gamma (IFN-gamma), a molecule which is pivotal in the expression of resistance to tuberculosis. Recent evidence demonstrates that infection with M. tuberculosis induces peripheral blood mononuclear cells to release the cytokine interleukin-12 (IL-12), a molecule that promotes the emergence of T-helper type-1 (Th1), IFN-gamma-producing T cells. We demonstrate here that IL-12 mRNA expression was induced by M. tuberculosis infection both in vivo and in vitro and that exogenous administration of IL-12 to mice transiently resulted in increased resistance to the infection. IL-12 also increased the production of IFN-gamma by both splenocytes derived from infected animals treated in vivo and by antigen-stimulated CD4 cells from untreated infected animals, with maximal effects at times associated with the expansion of antigen-specific CD4 T cells in vivo. In the absence of a T-cell response, as seen in SCID mice or nude mice, IL-12 only slightly augmented the moderate bacteriostatic capacity of these immunocompromised mice. Neutralization of IL-12 by specific monoclonal antibodies resulted in a reduction in granuloma integrity and slowing of the capacity of the animal to control bacterial growth.
Cooper
A M
AM
Department of Microbiology, Colorado State University, Fort Collins 80523, USA.
Roberts
A D
AD
Rhoades
E R
ER
Callahan
J E
JE
Getzy
D M
DM
Orme
I M
IM
D000818:Animals; D005260:Female; D015870:Gene Expression; D007111:Immunity, Cellular; D016867:Immunocompromised Host; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008099:Liver / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016513:Mice, SCID; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics; D013154:Spleen / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology
D012333:RNA, Messenger; D018664:Interleukin-12; D007371:Interferon-gamma