[Induced tolerance to cardiac allografts with multiple intravenous injection of donor spleen cells].
OBJECTIVE
To study the methods and mechanisms of immune tolerance in cardiac transplantation.


METHODS
Male DA rat hearts were transplanted to male Lewis rats using Ono's model and randomly divided into five groups: untreated, intravenous injection of 1 x 10(8) DA splenocytes to Lewis rat, intraperitoneal injection of cyclophosphamide (100 mg/kg) to Lewis rat, intravenous injection of 1 x 10(8) DA splenocytes combined with intraperitoneal injection of cyclophosphamide (100 mg/kg) to Lewis rat, multiple injection of DA rat splenocytes with intraperitoneal injection of cyclophosphamide, 11 days later heart transplantation was performed. Mean survival time (MST), histological changes, mixed lymphocyte reaction (MLR), the role of interleukin-2 (IL-2) to MLR and the role of tolerant rat splenocytes to MLR were measured after operation.


RESULTS
The survival time of heart allografts in the group of multiple injection of DA rat splenocytes with intraperitoneal injection of cyclophosphamide [MST: (85.3 +/- 7.5) d, t = 0, P < 0.01] was significantly longer than in the groups of untreated [MST: (7.3 +/- 1.0) d], intravenous injection of 1 x 10(8) DA splenocytes to Lewis rat [MST: (7.9 +/- 0.9) d], intraperitoneal injection of cyclophosphamide (100 mg/kg) to Lewis rat [MST: (8.1 +/- 1.2) d], intravenous injection of 1 x 10(8) DA splenocytes combined with intraperitoneal injection of cyclophosphamide (100 mg/kg) to Lewis rat [MST: (25.8 +/- 3.5) d]. Only a few inflammatory cells infiltrated in cardiac allografts in the group of multiple injection of DA rat splenocytes with intraperitoneal injection of cyclophosphamide. MLR in the group of multiple injection of DA rat splenocytes with intraperitoneal injection of cyclophosphamide were significantly decreased compared with those of normal control (t = 0, P < 0.01). IL-2 could partly reversed the hyporesponsiveness of MLR in tolerant rats, the tolerance could be transferred in vitro.


CONCLUSIONS
Multiple injection of donor splenocytes combined with intraperitoneal injection of cyclophosphamide to recipients could induce immune tolerance to cardiac allografts.
Department of Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
Hong-Wei
HW
Guo
Qing-Yu
QY
Wu
Shu-Sheng
SS
Xie
Qing-Yin
QY
Zhang
Xiu-Bin
XB
Yang
Meng-Ping
MP
Shao
D019264:Adoptive Transfer; D000818:Animals; D017690:Cell Transplantation; D003520:Cyclophosphamide / Q000494:pharmacology*; D006082:Graft Enhancement, Immunologic / Q000379:methods*; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology*; D007275:Injections, Intravenous; D007519:Isoantigens / Q000008:administration & dosage / Q000276:immunology; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D013154:Spleen / Q000166:cytology*; D023001:Transplantation Tolerance / Q000187:drug effects; D014183:Transplantation, Heterologous / Q000276:immunology
D007519:Isoantigens; D003520:Cyclophosphamide