| First Author | Thiessen S | Year | 2002 |
| Journal | Diabetes | Volume | 51 |
| Issue | 2 | Pages | 325-38 |
| PubMed ID | 11812739 | Mgi Jnum | J:74299 |
| Mgi Id | MGI:2158037 | Doi | 10.2337/diabetes.51.2.325 |
| Citation | Thiessen S, et al. (2002) T-cell tolerance by dendritic cells and macrophages as a mechanism for the major histocompatibility complex-linked resistance to autoimmune diabetes. Diabetes 51(2):325-38 |
| abstractText | For poorly understood reasons, the development of autoimmune diabetes in humans and mice is dominantly inhibited by major histocompatibility complex (MHC) class II molecules with diverse antigen-binding sites. We have previously shown that thymocytes expressing a highly diabetogenic I-A(g7)-restricted T-cell receptor (TCR) (4.1-TCR) undergo negative selection in mice carrying one copy of the antidiabetogenic H-2(b) haplotype in an I-A(b)-dependent but superantigen-independent manner. Here, we show that 4.1-TCR-transgenic thymocytes undergo different forms of tolerance in NOD mice expressing antidiabetogenic I-A(d), I-A(g7PD), or I-Ealpha(k) transgenes. The ability of protective MHC class II molecules to induce thymocyte tolerance in 4.1-TCR-transgenic NOD mice correlates with their ability to prevent diabetes in non-TCR-transgenic mice and is associated with polymorphisms within positions 56-67 of their beta1 domains. The 4.1-thymocyte tolerogenic activity of these MHC class II molecules is mediated by dendritic cells and macrophages but not by B-cells or thymic epithelial cells and is a peptide-dependent process. Antidiabetogenic MHC class II molecules may thus afford diabetes resistance by presenting, on dendritic cells and macrophages, tolerogenic peptides to a subset of highly diabetogenic and MHC-promiscuous CD4(+) T-cells that play a critical role in the initiation of diabetes. |
