INFLUENCE OF COMPLEMENT ON THE ALLOSPECIFIC ANTIBODY-RESPONSE TO A PRIMARY VASCULARIZED ORGAN GRAFT

The induction of antibody responses against T cell-dependent antigens has been reported to be influenced by complement. We therefore asked i f the primary induction of alloantibodies against transplantation anti gens, an important determinant of transplant outcome, is complement se nsitive and whether this has functional implications. We transplanted rat kidney allografts into fully major histocompatibility complex-mism atched recipients, in which complement activation was inhibited by dai ly 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 ra ts 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 t heir grafts contained less bound antibody than controls. Analysis beyo nd 6 days was obscured due to the development of antibodies against sC R1. We conclude that complement activation facilitates the induction o f the alloantibody response. Sparing of vascular injury and prolongati on of graft survival, previously reported in complement-inhibited rats (Pratt J. R. et al., Am. J. Path. 1996, 149: 2055), could therefore b e due to down-regulation of the B cell response as well as reduced com plement-dependent cytotoxicity. Inhibition of complement may provide a n ancillary approach to the prevention of allospecific antibody format ion and the prolongation of allograft survival in primary kidney graft ing.