IL-12 receptor regulation in IL-12-deficient BALB/c and C57BL/6 mice.
Immunization with protein antigen in complete Freund's adjuvant (CFA) induces Th1 cells in BALB/c and C57BL/6 (B6) mice. Pretreatment with the same protein in soluble form induces Th2 cells in BALB/c but not in B6 mice and inhibits Th1 cell development in both. We have previously shown that inhibition of Th1 in BALB/c mice correlates with the down-regulation of transcripts encoding the IL-12 receptor beta2 (IL-12Rbeta2) chain, which is required for IL-12 signaling and Th1 cell development. We now demonstrate that IL-12-deficient BALB/c mice, when primed with antigen in CFA, mount a Th2 instead of the Th1 response which develops in wild-type mice. Conversely, IL-12-deficient B6 mice fail to develop Th2 cells. Thus, a default Th2 development is induced by antigen priming in IL-12-deficient BALB/c but not B6 mice. IL-12Rbeta2 transcripts are still expressed in antigen-restimulated CD4(+) T cells from IL-12-deficient BALB/c and B6 mice and they are similarly reduced by pretreatment with soluble antigen, suggesting that intrinsic strain differences in IL-12R regulation do not account for the differential polarization to the Th2 pathway. IL-4 is not required for down-regulation of IL-12Rbeta2 transcripts and inhibition of Th1 development in mice pretreated with soluble protein, as shown by their reduction in IL-4-deficient BALB/c mice.
Galbiati
F
F
Roche Milano Ricerche, Milano, Italy.
Rogge
L
L
Adorini
L
L
D000818:Animals; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018123:Receptors, Interleukin / Q000235:genetics*; D053707:Receptors, Interleukin-12; D018417:Th1 Cells / Q000502:physiology; D018418:Th2 Cells / Q000502:physiology
C508443:Il12rb2 protein, mouse; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D016753:Interleukin-10; D018664:Interleukin-12