A heritable defect in IL-12 signaling in B10.Q/J mice. I. In vitro analysis

R. Ortmann, R. Smeltz, G. Yap, A. Sher, E. M. Shevach

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

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-γ. Because T cells from these mice could produce normal amounts of IFN-γ 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-γ when stimulated by IL-12. The capacity of NK cells, but not activated T cells, to produce IFN-γ in response to IL-12 could be partially restored by IL-18. The expression of the IL-12R β1- and β2-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.

Original languageEnglish (US)
Pages (from-to)5712-5719
Number of pages8
JournalJournal of Immunology
Volume166
Issue number9
DOIs
StatePublished - May 1 2001

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'A heritable defect in IL-12 signaling in B10.Q/J mice. I. In vitro analysis'. Together they form a unique fingerprint.

Cite this