The Journal of Immunology, 2007, 178: 102.10.
Copyright © 2007 by The American Association of Immunologists, Inc.
Adoptive therapy with allogeneic CD4+CD25+ Foxp3+ Treg cells induces transplantation tolerance
Dennis O Adeegbe,
Robert B Levy and
Thomas R Malek
Department of Microbiology & Immunology, Miller School of Medicine, University of Miami, 1600 NW 10th avenue, Miami, Florida, 33136
Abstract
Alloantigen primed Treg cells offer the potential for non-toxic suppression of transplant rejection reactions. If they are not rejected by the recipient, MHC-mismatched Treg cells might also establish transplant tolerance to the MHC molecules that the Treg cells were selected on during their development. In this regard, we have shown that the adoptive transfer of allogeneic Treg cells into neonatal IL-2R
–/–mice, which lack Treg cells and develop rapid lethal autoimmunity, lead to long-term engraftment by the donor Treg cells, effective prevention of this autoimmunity, and simultaneous long-term tolerance to the skin grafts expressing alloantigens shared by the Treg cells. This tolerance depended upon active suppression by Treg cells, not deletion or anergy. Mice tolerant to allogeneic C57BL/6 skin grafts were also tolerant to MHC class II-deficient C567BL/6 skin grafts, but rejected bm3 and bm12 skin grafts. These latter findings demonstrate that Treg cells are not required to directly recognize alloantigens within the skin grafts and that a single neo-antigen was sufficient to break tolerance. Collectively, these data demonstrate induction of dominant donor-specific transplantation tolerance by allogeneic Treg cells provided that the MHC antigens of both the Treg cells and transplant are matched.
(Supported by the NIH)
