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- Title
The role of interleukin-12 in acquired immunity to <em>Mycobacterium tuberculosis</em> infection.
- Authors
Williams, Richard O.; Ghrayeb, John; Feldmann, Marc; Maini, Ravinder N.
- Abstract
The early phase of acquired cellular immunity to Mycobacteriurn tuberculosis infection is mediated by the emergence of protective CD4 T lymphocytes that secrete cytokines including interferon-γ (IFN-γ), 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-γ-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-γ 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 immunocomprised 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.
- Subjects
B cells; LYMPHOCYTES; ANTIGEN presenting cells; LEISHMANIASIS; INTERLEUKINS; PROTOZOAN diseases
- Publication
Immunology, 1995, Vol 84, Issue 3, p423
- ISSN
0019-2805
- Publication type
Article