title: Memory CD4+T cells are suppressed by CD8+regulatory T cells in vitro and in vivo.
abstract: 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-γ 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-γ 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.
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Long
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Liang
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina Charleston, SC 29466, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Tomlinson
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina Charleston, SC 29466, USA.
authors.forename: Carl
authors.initials: C
authors.lastname: Atkinson
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Bixiang
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Chen
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhu
keywords: Qa-1; T regulatory cells (Tregs); memory T cells; transplantation