IL-12-deficient mice are defective but not devoid of type 1 cytokine responses.
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.
Magram
J
J
Department of Biotechnology, Hoffmann-La Roche, Nutley, New Jersey 07110, USA.
Sfarra
J
J
Connaughton
S
S
Faherty
D
D
Warrier
R
R
Carvajal
D
D
Wu
C Y
CY
Stewart
C
C
Sarmiento
U
U
Gately
M K
MK
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*
D016207:Cytokines; D018664:Interleukin-12; D007371:Interferon-gamma