INTERFERENCE WITH THE ALTERNATE PATHWAY OF COMPLEMENT ACTIVATION DURING TRANSPLANT REJECTION

Abstract

During the rejection of an allotransplant, there appears in the circulation a material which interferes with the alternate pathway of complement activation. This material also deposits on the graft and may be eluted and further purified by gel filtration. When added to normal human serum and zymosan, the rate of C3-C9 hemolytic consumption is retarded. This appears to result from an inhibition of the early steps in the alternate pathway leading to the initial generation of C3_b and activation of C3 proactivator. Thus, this material can prevent C3-C9 hemolytic consumption when added to a mixture of activated properdin convertase and normal human serum. Initial activation of properdin convertase by zymosan is not affected. Separation and culture of peripheral lymphocytes from patients rejecting a transplant show that there is elaboration of the material responsible for the interference with the alternate pathway activity. Removal of 85-95% of B cells by passage over antigen-antibody-complement coated columns does not prevent this generation suggesting that T cells may be responsible. This data may, therefore, represent evidence for a link between T cell function and the alternate pathway of complement activation in graft rejection. (Supported in part by N1AMD grant AM 17376)

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