B7-H4 Pathway in Islet Transplantation and β-Cell Replacement Therapies

Abstract EN

Type 1 diabetes (T1D) is a chronic autoimmune disease and characterized by absolute insulin deficiency.

β-cell replacement by islet cell transplantation has been established as a feasible treatment option for T1D.

The two main obstacles after islet transplantation are alloreactive T-cell-mediated graft rejection and recurrence of autoimmune diabetes mellitus in recipients.

T cells play a central role in determining the outcome of both autoimmune responses and allograft survival.

B7-H4, a newly identified B7 homolog, plays a key role in maintaining T-cell homeostasis by reducing T-cell proliferation and cytokine production.

The relationship between B7-H4 and allograft survival/autoimmunity has been investigated recently in both islet transplantation and the nonobese diabetic (NOD) mouse models.

B7-H4 protects allograft survival and generates donor-specific tolerance.

It also prevents the development of autoimmune diabetes.

More importantly, B7-H4 plays an indispensable role in alloimmunity in the absence of the classic CD28/CTLA-4 : B7 pathway, suggesting a synergistic/additive effect with other agents such as CTLA-4 on inhibition of unwanted immune responses.