IL-12-deficient mice are defective in IFN gamma production and type 1 cytokine responses.
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 IFN gamma following endotoxin administration and to mount a Th1 response in vivo, as measured by antigen-induced IFN gamma 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 IFN gamma 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.
Magram
J
J
Department of Biotechnology, Roche Institute of Molecular Biology, Nutley, New Jersey 07110, USA.
Connaughton
S E
SE
Warrier
R R
RR
Carvajal
D M
DM
Wu
C Y
CY
Ferrante
J
J
Stewart
C
C
Sarmiento
U
U
Faherty
D A
DA
Gately
M K
MK
D000818:Animals; D001483:Base Sequence; D005822:Genetic Vectors / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000172:deficiency* / Q000235:genetics*; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D008222:Lymphokines / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
D008222:Lymphokines; D018664:Interleukin-12; D007371:Interferon-gamma