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RETRACTED ARTICLE

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Immunity. 2003 Aug;19(2):243-55.

Autoimmunity as the consequence of a spontaneous mutation in Rasgrp1.

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1
Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

Abstract

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.

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PMID:
12932358
DOI:
10.1016/s1074-7613(03)00209-7
[Indexed for MEDLINE]
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