References
Query Results -- Details
MGI Accession ID: MGI:2176335
J Number: J:75331
Other Accession IDs:
Title: Hypo-active variant of IL-2 and associated decreased T cell activation contribute to impaired apoptosis in autoimmune prone MRL mice.
Authors: Choi Y; Simon-Stoos K; Puck J
Journal: Eur J Immunol
Volume: 32
Issue: 3
Date: 2002 Mar
Year: 2002
Pages: 677-85
Review Status: Peer Reviewed
Abstract:
Apoptosis of activated lymphocytes is crucial to the maintenance of immune homeostasis and self-tolerance, as demonstrated by the well-known autoimmune MRL lpr mouse lacking the deathreceptor Fas. However, even MRL+/+ activated T cells have a resistance to Fas-mediated apoptosis as compared to T cells from the non-autoimmune FVB/N strain. To understand the molecular mechanisms underlying these strain differences, we studied biochemical characteristics of T cells upon activation. Compared to FVB/N T cells, MRL T cells under-expressed procaspase-3 but over-expressed FLIP(L). In addition, up-regulation of Bcl-x(L), IL-2, and CD25 was diminished in MRL cells, suggesting inadequate T cell activation. Upon finding that MRL, like other autoimmune strains NOD and SJL, has a hypo-active variant of the IL-2 gene, we added wild-type murine recombinanat (mr)IL-2 during activation. Exogenous mrIL-2 restored MRL apoptosis to the level of FVB/N; in addition, expression of procaspase-3, and FLIP(L), Bcl-x(L) and CD25 was normalized. These results suggest that defective MRL T cell activation, in part due to hypo-active IL-2, underlies the impaired apoptosis of this strain. In addition, the hypo-active variant of IL-2 shared among autoimmune strains may, by causing diminished cell activation and cell death, predispose these strains to develop autoimmune disease.
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