| First Author | Kanagawa O | Year | 2000 |
| Journal | J Immunol | Volume | 164 |
| Issue | 10 | Pages | 5466-73 |
| PubMed ID | 10799914 | Mgi Jnum | J:62643 |
| Mgi Id | MGI:1859408 | Doi | 10.4049/jimmunol.164.10.5466 |
| Citation | Kanagawa O, et al. (2000) Thymic and postthymic regulation of diabetogenic CD8 T cell development in TCR transgenic nonobese diabetic (NOD) mice. J Immunol 164(10):5466-73 |
| abstractText | Natural development of diabetes in nonobese diabetic (NOD) mice requires both CD4 and CD8 T cells. Transgenic NOD mice carrying alphabeta TCR genes from a class I MHC (Kd)-restricted, pancreatic beta cell Ag-specific T cell clone develop diabetes significantly faster than nontransgenic NOD mice. In these TCR transgenic mice, a large fraction of T cells express both transgene derived and endogenous TCR beta chains. Only T cells expressing two TCR showed reactivity to the islet Ag. Development of diabetogenic T cells is inhibited in mice with no endogenous TCR expression due to the SCID mutation. These results demonstrate that the expression of two TCRs is necessary for the autoreactive diabetogenic T cells to escape thymic negative selection in the NOD mouse. Further analysis with MHC congenic NOD mice revealed that diabetes development in the class I MHC-restricted islet Ag-specific TCR transgenic mice is still dependent on the presence of the homozygosity of the NOD MHC class II I-Ag7. |
