Possible mechanism in rat with surviving heart allograft after short course of 15-deoxyspergualin treatment.
15-Deoxyspergualin has been reported to be a useful immunosuppressive agent, that is already used to inhibit acute rejection, in clinical transplantation. In the present study, the survival of heart allograft in rats after a short course of DSG treatment and the mechanism underlying induction of DSG-induced heart allograft survival, in the early phase, were studied. Male LEW rats were used as recipients. Male ACI and Wistar rats were used as donors and third party donors, respectively. Survival of ACI heart grafts in LEW recipients, treated with a short course of DSG, beginning from day 4 of grafting, were markedly prolonged, with a mean survival time of 16.6 +/- 5.8 days and 29.8 +/- 3.0 days at the dose of 2.5 mg/kg/day and 5 mg/kg/day, respectively. The mechanism of inducing allograft survival in the early phase, after a short course of DSG treatment, was further analyzed by testing the ability of splenic lymphocytes or serum in MLR assays and transfer experiments. The addition of various concentrations of splenic lymphocytes or serum from DSG treated LEW rat with surviving ACI heart allograft to MLR showed a strong suppression in a cell-dose-dependent manner and serum-dose-dependent manner, both in donor strain and third party MLR. An interesting finding was that there was a constant differential suppressive rate between donor strain party MLR and third party MLR. Moreover, transfer of 2.0 x 10(8) splenic lymphocytes or 2 ml serum from DSG-treated LEW rat with surviving ACI heart allograft, to sublethally irradiated grafted host, did not prolong survival both in ACI heart grafts and third party Wistar grafts. These results suggest that the strong suppresser cells and the suppressor humoral factor(s) play, at least, a partial role in the early phase of rats bearing allograft after a short course of DSG treatment.
Jiang
H
H
Department of Urology, Osaka University Medical School, Japan.
Takahara
S
S
Kyo
M
M
Takano
Y
Y
Kokado
Y
Y
Ishibashi
M
M
Sonoda
T
T
D000818:Animals; D006085:Graft Survival / Q000187:drug effects*; D006146:Guanidines / Q000494:pharmacology*; D016027:Heart Transplantation / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology
D006146:Guanidines; D007166:Immunosuppressive Agents; C037258:gusperimus