An examination of tissue chimerism in the ACI to Lewis rat cardiac transplant model.
While the existence of chimeric cells in host tissue following organ transplantation is well documented, its distribution, temporal evolution and relationship to allograft survival is less clear. To explore this phenomenon, Lewis recipients of ACI cardiac allografts representing a wide range of immunosuppressive protocols and graft survival times were examined for the presence of chimerism using a sensitive polymerase chain reaction assay. Four groups of animals were examined: untransplanted animals receiving donor specific transfusion (DST)/cyclosporine A (CsA); allograft recipients with no treatment; recipients treated with DST/CsA/supplementary immunosuppression with rejection at 21-183 days; and recipients sacrificed with functioning allografts, treated with DST/CsA/supplementary immunosuppression and surviving > 200 days. To elucidate variations in the tissue distribution of chimeric cells, bone marrow, skin, liver, spleen, and thymus were examined in each animal. Untransplanted animals receiving DST/CsA displayed no evidence of chimerism. In animals receiving a cardiac allograft but no treatment, there was extensive evidence of chimerism in four of five animals. Chimerism was also detected in seven of nine animals with intermediate graft survival at the time of rejection. In animals with long-term graft survival, only four of eight displayed chimerism. These results suggest that, without immunosuppression, early chimerism does not lead to prolonged graft survival and that, even when graft survival is moderately prolonged, these cells are not sufficient to prevent rejection. In conclusion, chimerism appears to be a common phenomenon following transplantation, is not a result of DST, and may not be necessary for maintenance of long-term graft survival.
Frede
S E
SE
University of Cincinnati Medical Center, Department of Surgery, Ohio 45267-0558, USA.
Levy
A E
AE
Alexander
J W
JW
Babcock
G F
GF
D000818:Animals; D006084:Graft Rejection / Q000175:diagnosis; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation / Q000502:physiology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D016133:Polymerase Chain Reaction; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D018183:Transplantation Chimera / Q000502:physiology; D014184:Transplantation, Homologous / Q000276:immunology
D007166:Immunosuppressive Agents