%0 Journal Article
%T Memory CD4+ T cells are suppressed by CD8+ regulatory T cells in vitro and in vivo
%A Bixiang Zhang
%A Carl Atkinson
%A Huifang Liang
%A Jian Wang
%A Jianping Zhao
%A Lin Chen
%A Peng Zhu
%A Qi Cheng
%A Stephen Tomlinson
%A Wei Wang
%A Xiaoping Chen
%A Xin Long
%J Archive of "American Journal of Translational Research".
%D 2017
%X Background: Acute graft rejection mediated by alloreactive memory CD4+ T cells is a major obstacle to transplantation tolerance. It has been reported that CD8+ T regulatory cells (Tregs) have the ability to induce graft tolerance by restraining the function of activated CD4+ T cells, but not including memory T cells. The aim of this study is to elucidate the effect of CD8+ Tregs on alloreactive memory CD4+ T cells. Methods: We detected Qa-1 expression and performed proliferative assay on memory CD4+ T cells. All memory CD4+ T cells were purified from mice receiving skin allografts. We performed inhibitory and cytotoxic assays on CD8+ Tregs, which were isolated from a T cell vaccination mouse model, and IL-2, IL-4, IL-10 and IFN-¦Ã levels were measured in co-culture supernatants by ELISA. To confirm CD8+ Tregs inhibition of memory CD4+ T cells in-vivo, we utilized a murine model of cardiac allograft transplantation. Results: Memory CD4+ T cells mediated acute allograft rejection, and CD8+ Tregs suppressed the proliferation of memory CD4+ T cells. In vitro, memory CD4+ T cells were inhibited and lysed by CD8+ Tregs. There was a positive correlation between IFN-¦Ã levels, and cell lysis rate induced by CD8+ Tregs. In-vivo studies demonstrated CD8+ Tregs prolonged graft survival times, by inhibiting CD4+ memory T cells, through a Qa-1-peptide-TCR pathway. Conclusions: CD8+ Tregs inhibit CD4+ memory T cell-mediated acute murine cardiac allograft rejection, and further prolong graft survival times. These results provide new insights into immune regulation of organ rejection
%K Qa-1
%K T regulatory cells (Tregs)
%K memory T cells
%K transplantation
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5250704/