CD4+CD25+ regulatory T cells-derived exosomes prolonged kidney allograft survival in a rat model

• Exosome is first released from CD4+CD25+ regulator T cells.
• Exosome can induce immune tolerance and prolong the survival time of recipients.
• In vitro, exosome possessed the capacity to suppress T cells proliferation.
• Exosome from B cells is also studied for comparison in supporting info.
• Exosome released from Treg might be one of far-end regulation mechanisms of Tregs.

CD4+CD25+ regulatory T cells (Tregs) are negative regulators of the immune system that induce and maintain immune tolerance. Exosomes are natural products released from many sources and play a role in antigen presentation, immunoregulation, and signal transduction. In order to determine whether exosomes can be released from Tregs and participate in transplantation tolerance, we isolated and purified Tregs-derived exosomes and established a rat model of kidney transplantation. We then transferred the autologous exosomes into recipients to observe the effect of transplantation tolerance in vivo and in vitro. From in vivo study, serum analysis and histology showed that the function of exosomes can postpone allograft rejection and prolong the survival time of transplanted kidney. From in vitro study, exosomes possessed the capacity to suppress T cells proliferation. Taken together, these results suggest that the Tregs-derived exosomes have a suppressive role on acute rejection and inhibit T cells proliferation, especially exosomes derived from donor-type Tregs, which imply that the Tregs-derived exosomes are one of far-end regulation mechanisms of Tregs. Thus, exosomes released from Tregs could be considered as a possible immunosuppressive reagent for the treatment of transplant rejection.