IL-12-deficient mice are defective but not devoid of type 1 cytokine responses

• Published in: Annals of the New York Academy of Sciences Vol. 795; p. 60
• Main Authors: Magram, J, Sfarra, J, Connaughton, S, Faherty, D, Warrier, R, Carvajal, D, Wu, C Y, Stewart, C, Sarmiento, U, Gately, M K
• Format: Journal Article
• Language: English
• Published: United States 01.10.1996
• Subjects: Animals; Cytokines - physiology; Interferon-gamma - biosynthesis; Interferon-gamma - physiology; Interleukin-12 - deficiency; Lymphocyte Activation; Mice; Mice, Knockout; T-Lymphocyte Subsets; Th1 Cells - physiology
• ISSN: 0077-8923
• DOI: 10.1111/j.1749-6632.1996.tb52655.x

Interleukin-12 (IL-12) has been described as a pivotal molecule in the immune response based in part on its ability to influence the differentiation of T helper (Th) cells into a type 1 (Th1) phenotype. This event is crucial in that appropriate differentiation of naive T cells can determine susceptibility or resistance to given pathogens by influencing the balance between cellular and humoral immunity. In order to further delineate the role of IL-12 in the immune response, we generated mice deficient for this cytokine. IL-12 knockout mice were viable, fully fertile, and displayed no obvious developmental abnormalities. Upon immunological analysis, these mice demonstrated an impaired ability to effect a Th1 response as well as an impaired ability to produce interferon-gamma in response to endotoxin in vivo. These data establish an essential role for IL-12 in the generation of optimal Th1 responses in vivo, but weak responses can occur independently of IL-12.