A combination of donor specific transfusion and rapamycin prolongs cardiac allograft survival in mice.
BACKGROUND
We sought to investigate the effects of donor-specific transfusion (DST) combined with rapamycin (RPM) on engraftment and demonstrate the mechanisms.


METHODS
B6 was treated with DST (on day -8) combined with RPM (from day -7 to -1, 1.5 microL/g per day). On day 0, B6 splenocytes were harvested to coculture with Balb/c splenocytes pretreated with mitomycin C in 1-way mixed lymphocyte cultures (MLC). After 48 hours, the proliferation, we measured apoptosis and the CD4(+)CD25(+) T-cell ratio of cultured cells. The heterotopic cardiac transplantation model was performed from Balb/c to B6 using the recipients pretreated with this protocol. On day 0, RPM was withdrawn and the transplantations performed. The mean survival time (MST) of the grafts evaluated and in vitro assays measured.


RESULTS
Both in vitro and in vivo, the protocol suppressed the proliferation of splenocytes as well as enhanced apoptosis and the CD4(+)CD25(+) T-cell ratio. The MST of the grafts was 35 +/- 14.4 days.


CONCLUSIONS
Our study showed that DST combined with RPM prolonged cardiac allograft survival even if we withdrew immunosuppressants after transplantation. This result may be associated with inhibition of T-cell proliferation. We also demonstrated that RPM expanded CD4(+)CD25(+) T cells and increased splenocyte apoptosis.
Wu
K
K
Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Wuhan, China.
Xiang
F
F
Yuan
J
J
Zeng
Z
Z
Zhou
H
H
Chang
S
S
Chen
Z K
ZK
D000818:Animals; D001803:Blood Transfusion; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003131:Combined Modality Therapy; D005434:Flow Cytometry; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020123:Sirolimus / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology; D014019:Tissue Donors; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D020123:Sirolimus