The role of interleukin-12 in acquired immunity to Mycobacterium tuberculosis infection

Autor: A M, Cooper, A D, Roberts, E R, Rhoades, J E, Callahan, D M, Getzy, I M, Orme
Rok vydání: 1995
Předmět:
Zdroj: Immunology. 84(3)
ISSN: 0019-2805
Popis: 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.
Databáze: OpenAIRE