Spontaneous acceptance of mouse kidney allografts is associated with increased Foxp3 expression and differences in the B and T cell compartments.

Spontaneous acceptance of organ allografts can identify novel mechanisms of drug-free transplantation tolerance. Spontaneous acceptance occurs in both mouse kidney transplants and rat liver transplants however the early immune processes of mouse kidney acceptance have not been studied. Acceptance of C57BL/6 strain kidney allografts in fully MHC-incompatible B10.BR recipients was compared with rejection (REJ) of heart allografts in the same strain combination. Graft infiltrate and antibody deposition were examined by immunohistochemical staining. Expression of mRNA was measured by quantitative real-time PCR. Apoptosis was examined by TUNEL staining. The majority of kidney allografts were accepted long-term and induced tolerance (TOL) of donor-strain skin grafts, showing that acceptance was not due to immune ignorance. There was an extensive infiltrate of T cells in the TOL kidney that exceeded the level in REJ hearts but subsequently declined. The main differences were deposition of IgG2a antibody in REJ that was absent in TOL, more B cells infiltrating TOL kidneys and a progressive increase in the ratio of CD8:CD4 cells during rejection. There was also significantly greater Foxp3 mRNA expression in TOL. Kidneys from RAG-/- donors were accepted, showing that donor lymphocytes were not necessary for acceptance. Neutralising antibodies to TGF-β administered from day 0 to day 6 did not prevent TOL. On the basis of cytokine expression and apoptosis there was no evidence for immune deviation or deletion as mechanisms of acceptance. In accord with the findings of spontaneous acceptance of liver allografts in rats, the main difference between mouse kidney TOL and heart REJ was in the B cell compartment. The major difference to rat liver allograft acceptance was that apoptosis of infiltrate did not appear to play a role. Instead, increased Foxp3 expression in TOL kidneys implies that regulatory T cells might be important.

Wang C ，Cordoba S ，Hu M ，Bertolino P ，Bowen DG ，Sharland AF ，Allen RD ，Alexander SI ，McCaughan GW ，Bishop GA ... -  《-》

Tolerance to rat liver allografts. I. Differences between tolerance and rejection are more marked in the B cell compared with the T cell or cytokine response.

Sun J ，McCaughan GW ，Matsumoto Y ，Sheil AG ，Gallagher ND ，Bishop GA ... -  《TRANSPLANTATION》

A short course of cyclosporine immunosuppression inhibits rejection but not tolerance of rat liver allografts.

Huang WH ，Yan Y ，De Boer B ，Bishop GA ，House AK ... -  《TRANSPLANTATION》

Reduction of Foxp3-expressing regulatory T cell infiltrates during the progression of renal allograft rejection in a mouse model.

Wang S ，Jiang J ，Guan Q ，Lan Z ，Wang H ，Nguan CY ，Jevnikar AM ，Du C ... -  《TRANSPLANT IMMUNOLOGY》

Cytokine mRNA profiles in mouse orthotopic liver transplantation. Graft rejection is associated with augmented TH1 function.

Thai NL ，Fu F ，Qian S ，Sun H ，Gao L ，Wang SC ，Demetris AJ ，Woo J ，Thomson AW ，Duquesnoy RJ ... -  《TRANSPLANTATION》