Published online Dec 15, 2014. doi: 10.4239/wjd.v5.i6.739
Revised: August 16, 2014
Accepted: September 6, 2014
Published online: December 15, 2014
Auto- and alloreactive T cells are major culprits that damage β-cells in type 1 diabetes (T1D) and islet transplantation. Current immunosuppressive drugs can alleviate immune-mediated attacks on islets. T cell co-stimulation blockade has shown great promise in autoimmunity and transplantation as it solely targets activated T cells, and therefore avoids toxicity of current immunosuppressive drugs. An attractive approach is offered by the newly-identified negative T cell co-signaling molecule B7-H4 which is expressed in normal human islets, and its expression co-localizes with insulin. A concomitant decrease in B7-H4/insulin co-localization is observed in human type 1 diabetic islets. B7-H4 may play protective roles in the pancreatic islets, preserving their function and survival. In this review we outline the protective effect of B7-H4 in the contexts of T1D, islet cell transplantation, and potentially type 2 diabetes. Current evidence offers encouraging data regarding the role of B7-H4 in reversal of autoimmune diabetes and donor-specific islet allograft tolerance. Additionally, unique expression of B7-H4 may serve as a potential biomarker for the development of T1D. Future studies should continue to focus on the islet-specific effects of B7-H4 with emphasis on mechanistic pathways in order to promote B7-H4 as a potential therapy and cure for T1D.
Core tip: Onset of type 1 diabetes is driven by defects in immune regulation, resulting in β-cell autoimmunity. However, there may be mechanisms inherent to the β-cell that may prevent or slow development of autoimmunity and progression of disease. One such factor is B7-H4, which acts at the islet-immune interface to defend β-cells from autoimmune diabetes and to protect transplanted islet allografts.