Dendritic cells expressing BTLA induces CD8+ T cell tolerance and attenuates the severity of diabetes

Numerous evidence demonstrate Type 1 diabetes (T1D) is due to a loss of immune tolerance to islet antigens, and CD8(+) T cells play an important role in the development of T1D in NOD mice. The novel coinhibitory receptor BTLA may have a regulatory role in maintaining peripheral tolerance, however, its role in autoimmune diabetes is unknown. To explore whether the generation of tolerance aiming at BTLA will help therapeutic intervention in T1D, the NOD mice were treated with genetically modified dendritic cells (DCs) expressing BTLA. The results demonstrated that transfer of modified DCs significantly induced CD8(+) T cell tolerance and attenuated the severity of diabetes. The findings suggest that genetically modified DC therapies enhancing the BTLA negative cosignal may prove valuable in treating T1D and other autoimmune diseases. (C) 2011 Elsevier Ltd. All rights reserved.