title: Promotion of allograft survival by CD4+CD25+ regulatory T cells: evidence for in vivo inhibition of effector cell proliferation.
abstract: Regulatory T cells preserve tolerance to peripheral self-Ags and may control the response to allogeneic tissues to promote transplantation tolerance. Although prior studies have demonstrated prolonged allograft survival in the presence of regulatory T cells (T-reg), data documenting the capacity of these cells to promote tolerance in immunocompetent transplant models are lacking, and the mechanism of suppression in vivo remains unclear. We used a TCR transgenic model of allograft rejection to characterize the in vivo activity of CD4(+)CD25(+) T-reg. We demonstrate that graft Ag-specific T-reg effectively intercede in the rejection response of naive T cells to established skin allografts. Furthermore, CFSE labeling demonstrates impaired proliferation of naive graft Ag-specific T cells in the draining lymph node in the presence of T-reg. These results confirm the efficacy of T-reg in promoting graft survival and suggest that their suppressive action is accomplished in part through inhibition of proliferation.
authors.affiliation: Harrison Department of Surgical Research, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Major K
authors.initials: MK
authors.lastname: Lee
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Moore
authors.forename: Beth P
authors.initials: BP
authors.lastname: Jarrett
authors.forename: Moh Moh
authors.initials: MM
authors.lastname: Lian
authors.forename: Shaoping
authors.initials: S
authors.lastname: Deng
authors.forename: Xiaolun
authors.initials: X
authors.lastname: Huang
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Markmann
authors.forename: Meredith
authors.initials: M
authors.lastname: Chiaccio
authors.forename: Clyde F
authors.initials: CF
authors.lastname: Barker
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Caton
authors.forename: James F
authors.initials: JF
authors.lastname: Markmann
mesh_terms: D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology; D015704:CD4 Antigens / Q000032:analysis*; D060908:CTLA-4 Antigen; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival; D016753:Interleukin-10 / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D016038:Skin Transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000502:physiology; D014184:Transplantation, Homologous
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D015704:CD4 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta; D016753:Interleukin-10