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5787766 
Journal Article 
BAFF regulates activation of self-reactive T cells through B-cell dependent mechanisms and mediates protection in NOD mice 
Mariño, E; Walters, SN; Villanueva, JE; Richards, JL; Mackay, CR; Grey, ST 
2014 
Yes 
European Journal of Immunology
ISSN: 0014-2980
EISSN: 1521-4141 
44 
4 
983-993 
English 
24435807 
WOS:000334174400010 
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.