The abrogation of allosensitization following the induction of mixed allogeneic chimerism.
The association of preformed anti-donor Abs with the hyperacute rejection of bone marrow and solid organ allografts and the persistence of the anti-donor immune response secondary to immunologic memory make allosensitization an absolute contraindication to transplantation. Mixed allogeneic (A + B-->A) bone marrow chimerism has been demonstrated to confer donor-specific tolerance in nonsensitized recipients, but has not been evaluated in the setting of allosensitization. The current study documents that despite significant anti-donor sensitization, mixed allogeneic engraftment is possible and provides a marked advantage over fully allogeneic (B-->A) models. Moreover, the acceptance of donor skin grafts and loss of circulating anti-donor Abs suggest that allosensitization can be abrogated with the induction of stable mixed allogeneic chimerism.
Colson
Y L
YL
Division of Pediatric Oncology, Dana-Farber Cancer Institute, and Division of Thoracic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Yolonda_Colson@dfci.harvard.edu
Schuchert
M J
MJ
Ildstad
S T
ST
D000818:Animals; D000918:Antibody Specificity / Q000235:genetics; D000961:Antilymphocyte Serum / Q000096:biosynthesis; D016026:Bone Marrow Transplantation / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology*; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics; D007114:Immunization / Q000379:methods; D007156:Immunologic Memory / Q000235:genetics; D007519:Isoantigens / Q000235:genetics / Q000276:immunology* / Q000528:radiation effects; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011828:Radiation Chimera / Q000276:immunology*; D016038:Skin Transplantation / Q000276:immunology
D000961:Antilymphocyte Serum; D007519:Isoantigens