| First Author | Chiu PP | Year | 2001 |
| Journal | J Immunol | Volume | 167 |
| Issue | 12 | Pages | 7169-79 |
| PubMed ID | 11739540 | Mgi Jnum | J:73098 |
| Mgi Id | MGI:2154570 | Doi | 10.4049/jimmunol.167.12.7169 |
| Citation | Chiu PP, et al. (2001) Genetic control of T and B lymphocyte activation in nonobese diabetic mice. J Immunol 167(12):7169-79 |
| abstractText | Type 1 diabetes in nonobese diabetic (NOD) mice is characterized by the infiltration of T and B cells into pancreatic islets. T cells bearing the TCR Vbeta3 chain are disproportionately represented in the earliest stages of islet infiltration (insulitis) despite clonal deletion of most Vbeta3(+) immature thymocytes by the mammary tumor virus-3 (Mtv-3) superantigen (SAg). In this report we showed that a high frequency of NOD Vbeta3(+) T cells that escape deletion are activated in vivo and that this phenotype is linked to the Mtv-3 locus. One potential mechanism of SAg presentation to peripheral T cells is by activated B cells. Consistent with this idea, we found that NOD mice harbor a significantly higher frequency of activated B cells than nondiabetes-prone strains. These activated NOD B cells expressed cell surface molecules consistent with APC function. At the molecular level, the IgH repertoire of activated B cells in NOD mice was equivalent to resting B cells, suggesting a polyclonal response in vivo. Genetic analysis of the activated B cell phenotype showed linkage to Idd1, the NOD MHC haplotype (H-2(g7)). Finally, Vbeta3(+) thymocyte deletion and peripheral T cell activation did not require B cells, suggesting that other APC populations are sufficient to generate both Mtv-3-linked phenotypes. These data provide insight into the genetic regulation of NOD autoreactive lymphocyte activation that may contribute to failure of peripheral tolerance and the pathogenesis of type I diabetes. |
