| First Author | Tolosa E | Year | 1998 |
| Journal | Immunity | Volume | 8 |
| Issue | 1 | Pages | 67-76 |
| PubMed ID | 9462512 | Mgi Jnum | J:45524 |
| Mgi Id | MGI:1195556 | Doi | 10.1016/s1074-7613(00)80459-8 |
| Citation | Tolosa E, et al. (1998) Thymocyte glucocorticoid resistance alters positive selection and inhibits autoimmunity and lymphoproliferative disease in MRL-lpr/lpr mice. Immunity 8(1):67-76 |
| abstractText | Thymus-derived glucocorticoids antagonize T cell receptor (TCR)-induced thymocyte apoptosis, allowing the survival (positive selection) of cells bearing TCRs that recognize self antigens with low-to-moderate avidity. Here we demonstrate that expression of an antisense glucocorticoid receptor transgene in thymocytes of spontaneously autoimmune MRL-lpr/lpr mice causes the loss of specific TCR Vbeta-bearing T cells that are normally positively selected in this strain. These transgenic mice had lower autoantibody production and milder symptoms of autoimmune disease than MRL-lpr/lpr controls and had markedly reduced accumulation of the TCR+Thy-1+CD4-CD8-B220+ T cells that are the hallmark of the lpr mutation. Thus, decreased glucocorticoid signaling in thymocytes alters the T cell repertoire and greatly diminishes autoimmunity in MRL-lpr/lpr autoimmune mice. |
