IL-12-Deficient Mice Are Defective in IFNγ Production and Type 1 Cytokine Responses

• Published in: Immunity (Cambridge, Mass.) Vol. 4; no. 5; pp. 471 - 481
• Main Authors: Magram, Jeanne, Connaughton, Suzanne E, Warrier, Rajeev R, Carvajal, Daisy M, Wu, Chang-you, Ferrante, Jessica, Stewart, Colin, Sarmiento, Ulla, Faherty, Denise A, Gately, Maurice K
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.1996
• Subjects: AIDS/HIV; Animals; Base Sequence; Genetic Vectors - immunology; Interferon-gamma - biosynthesis; Interleukin-12 - deficiency; Interleukin-12 - genetics; Killer Cells, Natural - immunology; Lymphocyte Activation - genetics; Lymphokines - biosynthesis; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Mutant Strains - growth & development; Mice, Mutant Strains - immunology; Mice, Mutant Strains - metabolism; Molecular Sequence Data; Th1 Cells - immunology; Th1 Cells - metabolism
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/S1074-7613(00)80413-6

IL-12 is a cytokine that can exert regulatory effects on T and NK cells and promote Th1 responses. To delineate further the physiologic role of IL-12 in immunity, mice deficient for this cytokine were generated. IL-12-deficient mice were impaired but not completely lacking in the ability to produce IFNγ following endotoxin administration and to mount a Th1 response in vivo, as measured by antigen-induced IFNγ secretion by immune lymph node cells in vitro. In contrast, secretion of IL-4 was enhanced, while proliferation and secretion of IL-2 and IL-10 were normal following antigen stimulation. DTH responses were significantly reduced in IL-12-deficient mice, but no defect in allogeneic CTL responses was observed. These results indicate that IL-12 plays an essential role in regulating IFNγ production and in facilitating normal DTH responses. However, other phenomena associated with Th1 responses and cell-mediated immunity, i.e., IL-2 secretion and CTL generation, were not compromised in the absence of IL-12.