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

Immunology. 1995 Mar;84(3):423-32.


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.

MeSH terms

  • Animals
  • Female
  • Gene Expression
  • Immunity, Cellular
  • Immunocompromised Host
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / genetics
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / genetics
  • Interleukin-12 / immunology*
  • Killer Cells, Natural / immunology
  • Liver / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Mice, SCID
  • Mycobacterium tuberculosis / isolation & purification
  • RNA, Messenger / genetics
  • Spleen / immunology
  • Tuberculosis / immunology*
  • Tuberculosis / microbiology
  • Tuberculosis / pathology


  • RNA, Messenger
  • Interleukin-12
  • Interferon-gamma