Promotion of allograft survival by CD4+CD25+ regulatory T cells: evidence for in vivo inhibition of effector cell proliferation.
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.
Lee
Major K
MK
Harrison Department of Surgical Research, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
Moore
Daniel J
DJ
Jarrett
Beth P
BP
Lian
Moh Moh
MM
Deng
Shaoping
S
Huang
Xiaolun
X
Markmann
Joseph W
JW
Chiaccio
Meredith
M
Barker
Clyde F
CF
Caton
Andrew J
AJ
Markmann
James F
JF
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
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