AbstractThe induction of antibody responses against T cell‐dependent antigens has been reported to be influenced by complement. We therefore asked if the primary induction of alloantibodies against transplantation antigens, an important determinant of transplant outcome, is complement sensitive and whether this has functional implications. We transplanted rat kidney allografts into fully major histocompatibility complex‐mismatched recipients, in which complement activation was inhibited by daily injection of soluble recombinant human complement receptor type 1 (sCR1). Control allograft recipients were injected with saline. Animals in the control group showed a marked antibody response against donor‐specific antigens and an increase in the proportion of activated B and T splenocytes by day 5 after transplantation. Complement‐inhibited rats showed a reduced level of antibody binding on target cells sharing the same histocompatibility antigens as the donor strain (p<0.001), and a reduced level of activated splenic B (p<0.01) and T (p<0.01) cells. In a functional assay, the plasma of complement‐inhibited rats showed reduced cytotoxic activity against donor‐specific cells, and their grafts contained less bound antibody than controls. Analysis beyond 6 days was obscured due to the development of antibodies against sCR1. We conclude that complement activation facilitates the induction of the alloantibody response. Sparing of vascular injury and prolongation of graft survival, previously reported in complement‐inhibited rats (Pratt J. R. et al.,Am. J. Path.1996,149: 2055), could therefore be due to down‐regulation of the B cell response as well as reduced complement‐dependent cytotoxicity. Inhibition of complement may provide an ancillary approach to the prevention of allospecific antibody formation and the prolongation of allograft survival in primar
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