Effect of donor antigen-trichosnthin conjugate in induction of mouse to rat cardiac xenografting tolerance.
OBJECTIVE
To investigate the special effect of donor antigen-trichosnthin (TCS) conjugate on depleting the immune reactive cells that respond to xenograft, and thus inducing specific xenograft tolerance.


METHODS
Rat anti-mouse antibodies coupled sepharose-4B beads were used to purify mouse H-2 antigens by affinity chromatography. Those purified H-2 antigens were conjugated with TCS by heterobifunctional reagents SPDP [3-(2-pyridyldithio) propionic acid-hydroxysuccinimide ester] and 2-IT (2-iminothiolane). The specific inhibition function of Ag-TCS to recipient's immune cells was measured in vitro. Ag-TCS conjugate (200 micrograms/kg, i.v.) was administered to the recipients (rats) 4 days prior to cardiac xenotransplantation of mouse to rat.


RESULTS
In vitro, the proliferation of immune reactive cells in the recipients pretreated with Ag-TCS was inhibited. The Ag-TCS conjugate significantly prolonged the cardiac survival time (6.88 +/- 1.36 days) compared with cyclosporine A (CsA) group (2.83 +/- 0.75 days) (P < 0.01).


CONCLUSIONS
Donor Ag-TCS conjugate can induce specific tolerance to xenograft.
Lan
P
P
Department of Surgery, First University Hospital, West China University of Medical Sciences, Chengdu 610041, China.
Zhan
W
W
Wang
J
J
Wang
J
J
D000818:Animals; D005260:Female; D006085:Graft Survival / Q000187:drug effects*; D006183:H-2 Antigens / Q000276:immunology*; D016027:Heart Transplantation; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D014183:Transplantation, Heterologous; D015978:Trichosanthin / Q000276:immunology / Q000494:pharmacology*
D006183:H-2 Antigens; D015978:Trichosanthin