Development of mouse CD4⁺CD25⁺Foxp3⁺ regulatory T cells in xenogeneic pig thymic grafts

Xenogeneic thymus transplantation is an effective strategy to induce tolerance to donors mainly by clonal depletion of reactive T cells. Recent studies have shown that functional mouse CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Treg) could efficiently populate in the periphery of athymic mice after grafting with neonatal pig thymus. However, it is still unknown whether xenogeneic thymus grafts could directly support the development of mouse CD4⁺CD25⁺Foxp3⁺ Treg cells as an autogeneic counterpart. Our results show that the percentages of mouse CD4⁺CD8^-CD25⁺ thymocytes are similar among auto- and xenogeneic thymic grafts in thymic mouse recipients. Mouse CD4⁺CD8^-CD25⁺ thymocytes maturing in xenogeneic thymic grafts exhibit similar expressions of Foxp3, TCR, CTLA-4 and GITR as those in autogeneic thymic grafts. Moreover, mouse CD4⁺CD8^-CD25⁺ thymocytes maturing in xenogeneic thymic grafts showed a significant immunosuppressive function on the proliferation of CD4⁺CD25^- T cells stimulated with Con A or allogeneic antigens, although they showed weaker effects than those maturing in autogeneic thymic grafts. Therefore, the present data provides direct evidence for the ability of xenogeneic porcine thymus grafts to support the development of mouse naturally occurring CD4⁺CD25⁺Foxp3⁺ Treg cells.