Membrane Properties and Functional Activity of Lymphocytes from Cyclophosphamide-Pretreated Rats

Abstract

In an attempt to explain the effect of drug pretreatment on the reduction of allograft immunogenicity, lymphocytes from normal and cyclophosphamide- (CY) pretreated rats were studied in leukocyte culture with phytohemagglutinin or allogeneic cells. Pretreatment with 250 mg/kg CY was associated with complete unresponsiveness as well as the inability to stimulate allogeneic cells. This was dose and time dependent and not explicable by just cell death in culture or drug carryover. CY-pretreated cells gave cytotoxic antibody titration curves suggestive of reduced but not absent surface histocompatibility antigens. Lymphocytes from normal and CY-pretreated rats did not show significant differences in the ability to form caps when reacted with antiimmunoglobulin antisera or in sensitivity to lysis in hypotonic solutions. Thus the cells from CY-pretreated rats appear to have surface alterations associated with the gene product of the MLR locus, decreased serologically detectable transplant antigens, and no serious defect in membrane fluidity or extensibility. This approach provides a potential monitoring system for donor pretreatment in organ allograft situations.