The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/7/39/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 1, July 7, 1997 39-45


Articles

Interleukin 12 (IL-12) Is Crucial to the Development of Protective Immunity in Mice Intravenously Infected with Mycobacterium tuberculosis

Andrea M. Cooper*, Jeanne Magram{ddagger}, Jessica Ferrante{ddagger}, and Ian M. Orme*

From the * Department of Microbiology, Colorado State University, Fort Collins, Colorado 80523; and the {ddagger} Department of Inflammation and Autoimmune Diseases, Hoffman-La Roche Incorporated, Nutley, New Jersey 07110

Immunity to Mycobacterium tuberculosis infection is associated with the emergence of protective CD4 T cells that secrete cytokines, resulting in activation of macrophages and the recruitment of monocytes to initiate granuloma formation. The cytokine-mediating macrophage activation is interferon-{gamma} (IFN-{gamma}), which is largely dependent on interleukin-12 (IL-12) for its induction. To address the role of IL-12 in immunity to tuberculosis, IL-12 p40–/– mice were infected with M. tuberculosis and their capacity to control bacterial growth and other characteristics of their immune response were determined. The IL-12 p40–/– mice were unable to control bacterial growth and this appeared to be linked to the absence of both innate and acquired sources of IFN-{gamma}. T cell activation as measured by delayed type hypersensitivity and lymphocyte accumulation at the site of infection were both markedly reduced in the IL-12 p40–/– mice. Therefore, IL-12 is essential to the generation of a protective immune response to M. tuberculosis, with its main functions being the induction of the expression of IFN-{gamma} and the activation of antigen-specific lymphocytes capable of creating a protective granuloma.


Address correspondence to Andrea M. Cooper, Department of Microbiology, Colorado State University, Fort Collins, Colorado 80524. Phone: 970-491-2833; FAX: 970-491-1815; E-mail: acooper{at}vines.colostate.edu

1Abbreviations used in this paper: DTH, delayed type hypersensitivity; ES, embryonic stem; HPRT, hypoxanthine phosphoribosyl transferase; PPD, purified protein derivative.


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