title: IL-12-deficient mice are defective but not devoid of type 1 cytokine responses.
abstract: 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.
authors.affiliation: Department of Biotechnology, Hoffmann-La Roche, Nutley, New Jersey 07110, USA.
authors.forename: J
authors.initials: J
authors.lastname: Magram
authors.forename: J
authors.initials: J
authors.lastname: Sfarra
authors.forename: S
authors.initials: S
authors.lastname: Connaughton
authors.forename: D
authors.initials: D
authors.lastname: Faherty
authors.forename: R
authors.initials: R
authors.lastname: Warrier
authors.forename: D
authors.initials: D
authors.lastname: Carvajal
authors.forename: C Y
authors.initials: CY
authors.lastname: Wu
authors.forename: C
authors.initials: C
authors.lastname: Stewart
authors.forename: U
authors.initials: U
authors.lastname: Sarmiento
authors.forename: M K
authors.initials: MK
authors.lastname: Gately
mesh_terms: D000818:Animals; D016207:Cytokines / Q000502:physiology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology; D018664:Interleukin-12 / Q000172:deficiency*; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets; D018417:Th1 Cells / Q000502:physiology*
chemical_list: D016207:Cytokines; D018664:Interleukin-12; D007371:Interferon-gamma