| First Author | Layer K | Year | 2003 |
| Journal | Immunity | Volume | 19 |
| Issue | 2 | Pages | 243-55 |
| PubMed ID | 12932358 | Mgi Jnum | J:85189 |
| Mgi Id | MGI:2673059 | Doi | 10.1016/s1074-7613(03)00209-7 |
| Citation | Layer K, et al. (2003) Autoimmunity as the consequence of a spontaneous mutation in Rasgrp1. Immunity 19(2):243-55 |
| abstractText | A mouse strain was identified with a recessive genetic lesion, which spontaneously developed a lymphoproliferative autoimmune syndrome exhibiting features of systemic lupus erythematosus. Positional mapping of the disease-associated locus revealed a lesion in Rasgrp1 that prevented the translation of the RasGRP1 protein. T cells from these mice failed to activate Ras or proliferate vigorously following antigen encounter and showed defects in positive selection. Peripheral RasGRP1lag T cells spontaneously adopted a memory phenotype and were able to transfer disease to lymphopenic recipient mice. CD4+ T cells accumulated in the lymphoid tissues of older RasGRP1lag mice and were resistant to activation-induced cell death. RasGRP1lag B cells were functionally normal, but activated B cells were detected in older mice, as were autoantibodies directed against self-antigens. Our findings indicate that Ras signaling pathways are required to maintain T cell tolerance and to prevent autoimmune disease. |
