| First Author | Ortmann R | Year | 2001 |
| Journal | J Immunol | Volume | 166 |
| Issue | 9 | Pages | 5712-9 |
| PubMed ID | 11313413 | Mgi Jnum | J:69051 |
| Mgi Id | MGI:1933938 | Doi | 10.4049/jimmunol.166.9.5712 |
| Citation | Ortmann R, et al. (2001) A heritable defect in IL-12 signaling in B10.Q/J mice. I. In vitro analysis. J Immunol 166(9):5712-9 |
| abstractText | B10.Q mice are normally susceptible to the induction of collagen-induced arthritis. We noted that one subline of B10.Q mice, B10.Q/J, was completely resistant to disease induction when immunized with collagen in CFA. B10.Q/J mice have a global defect in the generation of Th1 responses, and Ag-specific T cells derived from this strain failed to produce IFN-gamma. Because T cells from these mice could produce normal amounts of IFN-gamma when activated by IL-12/IL-18-independent stimuli, the defect appeared to be a failure to respond to IL-12. This defect extended to NK cells, which also failed to produce IFN-gamma when stimulated by IL-12. The capacity of NK cells, but not activated T cells, to produce IFN-gamma in response to IL-12 could be partially restored by IL-18. The expression of the IL-12R beta1- and beta2-chains on T cells and NK cells from B10.Q/J mice was normal. However, activated T cells from B10.Q/J mice did not signal normally through the IL-12R and manifested a defect in their capacity to phosphorylate Stat4. This defect was partial in that it could be overcome by increasing both the concentration of IL-12 and the incubation times in the Stat4 phosphorylation assays. Because Stat4 function is apparently intact in B10.Q/J mice, the defect in IL-12 signaling can be localized between the IL-12R complex and Stat4. This subtle abnormality in IL-12 responsiveness results in a profound defect in the generation of Th1 cells and the development of autoimmune disease. |
