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Publication : Host APCs augment in vivo expansion of donor natural regulatory T cells via B7H1/B7.1 in allogeneic recipients.

First Author  Yi T Year  2011
Journal  J Immunol Volume  186
Issue  5 Pages  2739-49
PubMed ID  21263067 Mgi Jnum  J:169409
Mgi Id  MGI:4940941 Doi  10.4049/jimmunol.1002939
Citation  Yi T, et al. (2011) Host APCs Augment In Vivo Expansion of Donor Natural Regulatory T Cells via B7H1/B7.1 in Allogeneic Recipients. J Immunol 186(5):2739-49
abstractText  Foxp3(+) regulatory T (Treg) cells include thymic-derived natural Treg and conventional T-derived adaptive Treg cells. Both are proposed to play important roles in downregulating inflammatory immune responses. However, the mechanisms of Treg expansion in inflammatory environments remain unclear. In this study, we report that, in an autoimmune-like graft-versus-host disease model of DBA/2 (H-2(d)) donor to BALB/c (H-2(d)) recipients, donor Treg cells in the recipients predominantly originated from expansion of natural Treg cells and few originated from adaptive Treg cells. In vivo neutralization of IFN-gamma resulted in a marked reduction of donor natural Treg expansion and exacerbation of graft-versus-host disease, which was associated with downregulation of host APC expression of B7H1. Furthermore, host APC expression of B7H1 was shown to augment donor Treg survival and expansion. Finally, donor Treg interactions with host APCs via B7.1/B7H1 but not PD-1/B7H1 were demonstrated to be critical in augmenting donor Treg survival and expansion. These studies have revealed a new immune regulation loop consisting of T cell-derived IFN-gamma, B7H1 expression by APCs, and B7.1 expression by Treg cells.
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