title: Mesenchymal stem cells differentially mediate regulatory T cells and conventional effector T cells to protect fully allogeneic islet grafts in mice.
abstract: OBJECTIVE
  Limited information is available on the cellular interactions between regulatory T (T(reg)) cells and mesenchymal stem cells (MSCs). In particular, a direct effect of MSCs on the survival and proliferation of T(reg) cells has not been demonstrated.
  
  
  METHODS
  We investigated the effects of MSCs on effector T (T(eff)) cells and T(reg) cells, and the molecular mechanisms involved in the distinct regulation of these two cell populations by MSCs in vivo and in vitro.
  
  
  RESULTS
  We show that MSCs are capable of selectively suppressing T(eff) cells and fostering the generation of T(reg) cells. T(eff) cells, but not T(reg) cells, fail to respond to IL-2 and undergo profound apoptosis in the presence of MSCs. The differential regulations of these two T cell subsets by MSCs are associated with their distinct expressions of CD25, with MSCs specifically reducing the expression of CD25 on T(eff) and sparing T(reg) cells intact. In vivo, the administration of MSCs significantly delays the rejection of allogeneic islet grafts in adaptive transferred recipients by favouring the induction of T(reg) cells. In this model, MSCs inhibit the proliferation and development of alloreactive T(eff) but potently enhance the induction of T(reg) cells.
  
  
  CONCLUSIONS
  We demonstrate that MSCs are capable of regulating T(eff) and T(reg) cells differentially in vitro. MSCs inhibit T(eff) cells by inducing apoptosis and impairing the proliferative response to IL-2 in T(eff) cells, but favour the survival and expansion of T(reg) cells. This result is further demonstrated in mice that have undergone allogeneic islet transplantation, in which MSCs suppress alloreactive T(eff) cells while favouring the induction of T(reg) cells, thus protecting the islet allografts from rejection.
authors.affiliation: Department of Haematology, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: D M
authors.initials: DM
authors.lastname: Xu
authors.forename: X F
authors.initials: XF
authors.lastname: Yu
authors.forename: D
authors.initials: D
authors.lastname: Zhang
authors.forename: M X
authors.initials: MX
authors.lastname: Zhang
authors.forename: J F
authors.initials: JF
authors.lastname: Zhou
authors.forename: P H
authors.initials: PH
authors.lastname: Tan
authors.forename: Y C
authors.initials: YC
authors.lastname: Ding
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000601:surgery*; D006085:Graft Survival / Q000276:immunology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*