| First Author | Wu C | Year | 2000 |
| Journal | J Immunol | Volume | 165 |
| Issue | 11 | Pages | 6221-8 |
| PubMed ID | 11086056 | Mgi Jnum | J:65891 |
| Mgi Id | MGI:1927423 | Doi | 10.4049/jimmunol.165.11.6221 |
| Citation | Wu Cy, et al. (2000) IL-12 receptor ss2 (IL-12Rss2)-deficient mice are defective in IL-12-mediated signaling despite the presence of high affinity IL-12 binding sites. J Immunol 165(11):6221-8 |
| abstractText | Two subunits of the IL-12 receptor (IL-12R), IL-12Rss1 and IL-12Rss2, have been identified and cloned. Previous studies demonstrated that the IL-12Rss1 subunit was required for mouse T and NK cells to respond to IL-12 in vivo. To investigate the role of IL-12Rss2 in IL-12 signaling, we have generated IL-12Rss2-deficient (IL-12Rss2(-/-)) mice by targeted mutation in embryonic stem (ES) cells. Although Con A-activated splenocytes from IL-12Rss2(-/-) mice still bind IL-12 with both high and low affinity, no IL-12-induced biological functions can be detected. Con A-activated splenocytes of IL-12Rss2(-/-) mice failed to produce IFN-gamma or proliferate in response to IL-12 stimulation. NK lytic activity of IL-12Rss2(-/-) splenocytes was not induced when incubated with IL-12. IL-12Rss2(-/-) splenocytes were deficient in IFN-gamma secretion when stimulated with either Con A or anti-CD3 mAb in vitro. Furthermore, IL-12Rss2(-/-) mice were deficient in vivo in their ability to produce IFN-gamma following endotoxin administration and to generate a type 1 cytokine response. IL-12-mediated signal transduction was also defective as measured by phosphorylation of STAT4. These results demonstrate that although mouse IL-12Rss1 is the subunit primarily responsible for binding IL-12, IL-12Rss2 plays an essential role in mediating the biological functions of IL-12 in mice. |
