Increased CD4+ Foxp3+ T cells reflect immune response but not transplant tolerance

Objective To investigate the mechanism underlying the development of CD4+ Foxp3+ regulatory T cells(Tregs)in transplantation and their potential role in immune system. Methods Transplant tolerant mice were established by neonatal infusion with donor cells.Chimerism, alloreactive T cells, and Tregs of the mice were examined.Adoptive transfer experiments were used to analyze the development of Tregs in alloimmune response. Results The frequency of Tregs was the same in naive as in neonatal tolerant mice, while alloreactive T cells were selectively depleted in the latter.When lymphocytes from naive mice were adoptively transferred into syngenic tolerant mice, transferred alloreactive T cells destroyed chimerism and sustained skin grafts in recipients and induced an increase of Tregs in both transferred alloreactive T cells and host derived non-alloreactive T cells. Conclusion Tregs, which were induced in immune response in an antigen-independent manner, may regulate immune response as a negative feedback. Key words: Transplant tolerance; CD4+ Fxop3+ T cells; Graft rejection; Alloreactive T cells