Tolerance in mixed chimerism - a role for regulatory cells?
The establishment of mixed hematopoietic chimerism induces life-long donor-specific organ graft tolerance while obviating the need for chronic immunosuppression. Recent advances have dramatically reduced the conditioning toxicity required to achieve mixed chimerism. We argue that the achievement of high levels of donor chimerism ensures life-long deletion of donor-reactive T cells, precluding and obviating the need for regulatory mechanisms in the maintenance of tolerance. However, in situations where high levels of donor chimerism cannot be established or sustained, control of immune responsiveness can be achieved through additional mechanisms, including regulatory T cells.
Kurtz
Josef
J
Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, MGH East, Bldg. 149-5102 13(th) Street, Boston, MA 02129, USA.
Wekerle
Thomas
T
Sykes
Megan
M
D006085:Graft Survival / Q000276:immunology; D018448:Models, Immunological; D013601:T-Lymphocytes / Q000276:immunology; D018183:Transplantation Chimera / Q000276:immunology*; D019172:Transplantation Conditioning / Q000379:methods*; D023001:Transplantation Tolerance / Q000276:immunology* / Q000502:physiology*