Regulatory T Cell-mediated Immune Microenvironment Changes Promote Tumor Growth In Graft Liver After Mice Liver Transplantation

Background and Objectives:It is currently known that regulatory T cells (Tregs) play an important role in transplantation and tumor immunity. Due to the lack of suitable animal models, the exact impact of regulatory T cells on liver tumors after liver transplantation (LT) is not known. Our study revealed the impact of Treg-mediated immune micro-environment changes on liver metastases after mLT.Methods:We performed a tumor metastatic experiment on mouse liver transplantation (mLT) model to determine the impact of Tregs on liver metastasis; Tumor-lymphocyte co-culture experiments were used to detect differences of tumor-killing ability between two group; A series of immunohistochemical staining was used to detect liver transplant infiltrating lymphocyte; RT-PCR and ELISA was used to detect the expression of Tregs and Teffs’key regulatory; in-vivo function of Tregs and Teffs was analysis by flow cytometry intracellular staining; in vitro lymphocytes co-coulture (Tregs-Teffs) test and adoptive immunotherapy experiments in tumor-bearing nude-mice was used to verify the impaction of Tregs on Teffs proliferation/apoptosis and tumor-killing capacity.Results:MHC-mismatched mLT promote liver metastases due to the impiration of effect T cell (Teffs) function; The number of graft-infiltrating Tregs was significantly increased compared with syngenetic mLT; MHC-mismatched mLT increase the expreesion of Tregs’key regulator factors; in vitro or in vivo studys both show that Tregs from Allogenic group not only can signicantly promote apoptosis of Teff, but also inhibit the thire proliferation.Conclusions:The results showed that through weakening the immune function of effector T cells and promoted their apoptosis, Tregs provided immune protection for tumor groth after mLT.