| First Author | Hall HT | Year | 2008 |
| Journal | Eur J Immunol | Volume | 38 |
| Issue | 11 | Pages | 3191-9 |
| PubMed ID | 18925576 | Mgi Jnum | J:143267 |
| Mgi Id | MGI:3826303 | Doi | 10.1002/eji.200838259 |
| Citation | Hall HT, et al. (2008) Increased diabetes development and decreased function of CD4+CD25+ Treg in the absence of a functional DAP12 adaptor protein. Eur J Immunol 38(11):3191-9 |
| abstractText | Prior to the development of type 1 diabetes, T cells are primed in the pancreatic lymph nodes (PLN) where they interact with APC displaying beta cell-derived peptides. The details concerning the regulation of autoreactive T cell responses in the PLN are unclear. BDC2.5/B6g7 TCR transgenic mice represent a simplified model of type 1 diabetes, in which beta cell-specific CD4+ T cells expressing a diabetogenic transgenic TCR are first activated in the PLN and subsequently home to the pancreas where they mediate killing of beta cells. DNAX-activating protein of 12 kDa (DAP12) is an adaptor molecule carrying an ITAM motif. It associates with receptors on lymphoid and myeloid cells, including APC. We here show that introduction of a DAP12 null mutation in BDC2.5/B6g7 mice accelerated diabetes development and promoted an augmented activation state of PLN T cells expressing the transgenic TCR. Transferred BDC2.5 T cells proliferated more efficiently in the PLN of DAP12-deficient B6g7 recipients, which correlated with a decreased impact of co-transferred BDC2.5+CD4+CD25+ T cells. We propose that signaling through a DAP12-associated receptor on APC facilitates activation of Treg in the PLN and by this contributes to the maintenance of peripheral tolerance to beta cell-derived antigens. |
