| First Author | Mariño E | Year | 2014 |
| Journal | Eur J Immunol | Volume | 44 |
| Issue | 4 | Pages | 983-93 |
| PubMed ID | 24435807 | Mgi Jnum | J:209374 |
| Mgi Id | MGI:5567033 | Doi | 10.1002/eji.201344186 |
| Citation | Marino E, et al. (2014) BAFF regulates activation of self-reactive T cells through B-cell dependent mechanisms and mediates protection in NOD mice. Eur J Immunol 44(4):983-93 |
| abstractText | Targeting the BAFF/APRIL system has shown to be effective in preventing T-cell dependent autoimmune disease in the NOD mouse, a spontaneous model of type 1 diabetes. In this study we generated BAFF-deficient NOD mice to examine how BAFF availability would influence T-cell responses in vivo and the development of spontaneous diabetes. BAFF-deficient NOD mice which lack mature B cells, were protected from diabetes and showed delayed rejection of an allogeneic islet graft. Diabetes protection correlated with a failure to expand pathogenic IGRP-reactive CD8(+) T cells, which were maintained in the periphery at correspondingly low levels. Adoptive transfer of IGRP-reactive CD8(+) T cells with B cells into BAFF-deficient NOD mice enhanced IGRP-reactive CD8(+) T-cell expansion. Furthermore, when provoked with cyclophosphamide, or transferred to a secondary lymphopenic host, the latent pool of self-reactive T cells resident in BAFF-deficient NOD mice could elicit beta cell destruction. We conclude that lack of BAFF prevents the procurement of B-cell-dependent help necessary for the emergence of destructive diabetes. Indeed, treatment of NOD mice with the BAFF-blocking compound, BR3-Fc, resulted in a delayed onset and reduced incidence of diabetes. |
