| First Author | Choi Y | Year | 2002 |
| Journal | Eur J Immunol | Volume | 32 |
| Issue | 3 | Pages | 677-85 |
| PubMed ID | 11857342 | Mgi Jnum | J:75331 |
| Mgi Id | MGI:2176335 | Doi | 10.1002/1521-4141(200203)32:3<677::AID-IMMU677>3.0.CO;2-I |
| Citation | Choi Y, et al. (2002) Hypo-active variant of IL-2 and associated decreased T cell activation contribute to impaired apoptosis in autoimmune prone MRL mice. Eur J Immunol 32(3):677-85 |
| abstractText | 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. |
