Factors involved in rejection of concordant xenografts in complement-deficient rats.
BACKGROUND
Factors that contribute to xenograft (Xg) rejection were investigated in complement C6-deficient (C-) PVG rats.


METHODS
First and second hamster hearts were transplanted in C6-deficient and C6-sufficient PVG rats. Xenoantibody (XAb) formation, hemolytic C (CH50) activity and immunohistochemistry were studied.


RESULTS
PVG C6-deficient rats rejected Xgs 3 days later than PVG C6-sufficient rats. Surprisingly, C activation participated in the rejection in PVG C- rats, as shown by partially recovered serum CH50 levels and deposition of C factors in the Xgs. As we found that cultured endothelial cells produced C6 in vitro, we hypothesized that Xg endothelial cells corrected the C6 defect in PVG C- rats. This was probably induced by IgM XAbs as: (1) it did not occur in immunosuppressed PVG C- rats in which XAb formation was prevented, and (2) transfer of IgM XAbs to naive, xenotransplanted PVG C- rats accelerated the recovery of CH50 and concomitantly Xg rejection. Thirty days after rejection of a first Xg, when no IgM XAbs or CH50 activity but high levels of IgG XAbs were detected in PVG C- rats, second Xgs underwent a hyperacute rejection. This time, complement was not involved, as no serum CH50 nor C deposition was found in the Xg. Instead, IgG antibody-dependent cellular cytotoxicity was involved as: (1) IgG XAbs were deposited in the Xg and (2) hyperacute rejection was induced in naive PVG C- rats by transfer of IgG XAbs, and (3) this rejection was delayed to 5+/-3 days if the adoptive hosts were first irradiated.


CONCLUSIONS
In the face of a defect of host C factors, IgM XAb may induce cells of the Xg to secrete C factors which may correct the C defect of the host. Even if activation of lytic C can be prevented, IgG XAb may still provoke an acute Xg rejection by antibody-dependent cellular cytotoxicity.
Lin
Y
Y
Rega Institute, Division of Nephrology, University of Leuven, Belgium.
Vandeputte
M
M
Waer
M
M
D000818:Animals; D002478:Cells, Cultured; D003183:Complement C6 / Q000172:deficiency* / Q000502:physiology; D015938:Complement Membrane Attack Complex / Q000502:physiology; D006224:Cricetinae; D019084:Fluorescent Antibody Technique, Indirect; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D051381:Rats; D014183:Transplantation, Heterologous
D003183:Complement C6; D015938:Complement Membrane Attack Complex