| First Author | Yadav D | Year | 2007 |
| Journal | Mol Immunol | Volume | 44 |
| Issue | 10 | Pages | 2616-24 |
| PubMed ID | 17289146 | Mgi Jnum | J:118681 |
| Mgi Id | MGI:3700101 | Doi | 10.1016/j.molimm.2006.12.008 |
| Citation | Yadav D, et al. (2007) B7-1 mediated costimulation regulates pancreatic autoimmunity. Mol Immunol 44(10):2616-24 |
| abstractText | Costimulation by B7-1 and B7-2 molecules results in divergent biological effects. This is particularly striking in the NOD mouse, since the lack of B7-2 leads to complete protection from diabetes whereas the B7-1 deficiency causes exacerbation of disease. We tested the hypothesis that B7-1 costimulation suppresses pancreatic autoimmunity. We describe that the lack of B7-1 not only causes aberrant thymocyte maturation but also significantly enhances expansion, survival, and effector function of islet specific T cells in periphery. We also observed a significant reduction in the proportion of T-regulatory (T-regs) cells. Immunophenotypic analysis of T and APCs revealed a significantly lower frequency of T cells expressing the negative costimulatory receptor PD-1 in B7-1KO mice whereas the proportion of B7-H1 positive APCs was found to be significantly higher. Blocking studies in B7-1KO mice suggest that B7-H1 provides negative signals for anti islet CD4 and CD8 T-cell expansion but is differentially required for their priming. Our data demonstrate that deficiency of B7-1 mediated costimulation causes multitude of immunological defects, which involve reduction in T-regs and a concomitant enhancement of expansion, survival and effector potential of auto reactive T cells. |
