The impact of CD4+ CD25+ regulatory T cells on the mouse spontaneous liver transplant tolerance

Objective To examine the contribution of CD4^＋CD25^＋ regulatory T cells to liver transplant tolerance. Methods After injection of anti-CD25 monoclonal antibody （mAb, PC61）, mouse orthotopic liver transplantation was performed and survivals were determined. The paraffin-embedded sections of hepatic allografts were cut and stained with hematoxylin and eosin （HE）. Furthermore, the effect ofCD4^＋CD25^＋regulatory T cells on proliferative response of CD4^＋ T cells and cyto toxicity of CD8^＋ T ceils was examined by depleting these regulatory T cells. Results Depletion of these cells in the recipients but not in the donors before liver transplantation caused rejection. Histological analyses of hepatic allografts with PC61 treatment showed extensive leukocyte infiltration and tissue destruction, whereas those in the control group showed minimal changes. Moreover, elimination of CD4^＋CD25^＋ T cells resulted in the enhancement of both proliferative response of CD4^＋ T cells and eytotoxicity of CD8^＋ T cells against donor-type alloantigen. Conclusions These results suggest that CD4^＋CD25^＋regulatory T cells were important for tolerance induction to hepatic allografts. Key words: CD4^＋CD25^＋regulatory T cells;  Liver transplantaton;  Immunologieal tolerance