T-reg mediated suppression of the allograft response in the draining lymph node.
We previously demonstrated that T-regs inhibit proliferation of graft-reactive T cells in the draining lymph node (DLN), suggesting that this site may be important for regulation. TCR transgenic mice (TS1) specific for viral hemagglutinin (HA) provided antigen-specific T cells for adoptive transfer into syngeneic Balb/c hosts bearing HA+ skin grafts. T-regs were obtained from (TS1xHA28)F1 mice known to have an expanded population of HA-specific T-regs. To determine whether the lymph node is an independent site of suppression, we developed a model in which donor antigen that migrates from the allograft to the DLN drives T-cell activation after graft removal. T-regs that did not encounter the allograft itself remained able to inhibit graft antigen-specific T-cell proliferation in the DLN. Alloantigen-induced regulation can occur in the absence of the graft. This finding identifies the DLN as a potentially critical site of regulation in the early posttransplant period.
Lee
Major K
MK
Department of Surgery, Hospital of the University of Pennsylvania, PA 19104, USA.
Moore
Daniel J
DJ
Chiaccio
Meredith
M
Lian
Moh Moh
MM
Deng
Shaoping
S
Mohiuddin
Muhammad
M
Huang
Xiaolun
X
Koeberlein
Brigitte
B
Zakheim
Adam
A
Porrett
Paige M
PM
Barker
Clyde F
CF
Caton
Andrew J
AJ
Markmann
James F
JF
D000818:Animals; D007165:Immunosuppression Therapy; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D015375:Receptors, Interleukin-2 / Q000097:blood; D016038:Skin Transplantation / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D023001:Transplantation Tolerance / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology*
D015375:Receptors, Interleukin-2