FoxP3+, and not CD25+, T cells increase post-transplant in islet allotransplant recipients following anti-CD25+ rATG immunotherapy

Anti-CD25 antibodies are used as an induction therapy in islet allotransplantation for type 1 diabetes. Although previous reports suggested that anti-CD25 treatment may lead to depletion of CD4+CD25+ regulatory T cells (Tregs) and questioned its use in tolerance-promoting protocols for transplantation, the effect of anti-CD25 antibodies on the frequency and function of Tregs remains unclear. We examined the effect of anti-CD25 antibody, daclizumab, in vivo on Tregs in islet allograft recipients enrolled in a single-center study and monitored post-transplant. Our data shows that the reduction in CD25+ Treg cells observed post-transplant is due to masking of CD25 receptor by daclizumab and not due to depletion. In addition, using Treg marker, FoxP3, we show that anti-CD25+ ATG treatment leads to an increase in FoxP3+ Tregs post-transplant. These data suggest that anti-CD25-based therapy has beneficial effects on Tregs and combined with ATG may be a promising therapy for autoimmunity and transplantation.

► We examined the effects of induction therapy on Tregs in islet allotransplant.
► Detection of CD25+ cells is masked but not deleted by anti-CD25 treatment.
► Anti-CD25 does not adversely affect survival of Tregs in vitro and in vivo.
► Anti-CD25 therapy synergizes with ATG to promote expansion of FoxP3+ Tregs in vivo.
► This is an attractive combination for establishing transplantation tolerance.