INHIBITION OF THE HUMAN MIXED LYMPHOCYTE CULTURE (MLC) INTERACTION BY CYTOTOXIC AGENTS CONJUGATED TO ANTI-LYMPHOCYTE GLOBULIN

Abstract

Publisher Summary This chapter discusses the inhibition of the human mixed lymphocyte culture (MLC) interaction by cytotoxic agents conjugated to anti-lymphocyte globulin. The idea of linking cytotoxic drugs to antilymphocyte globulin is an attractive one with the aim of producing a more selective form of immunosuppression following allografting in vivo . A study described in the chapter coupled horse antihuman antilymphocyte globulin (ALG) to two cytotoxic alkylating agents and analyzed the effects of these complexes on the proliferative response in human mixed lymphocyte cultures. Both types of complexes proved highly inhibitory in the absence of complement and were significantly more potent than ALG or drug alone. For ALG–Chlorambucil complex, the method of complexing chlorambucil (Chlor) to IgG in alkaline solution described by O’Neil and Davis was used. This type of linkage is a physical one and in all probability dissociates in vivo or in vitro at 37°C. The chapter describes the effects of preincubating MLC responding cells with various concentrations of drug, ALG or ALG–Drug complexes. Lymphocytes preincubated with ALG–PGA–Mel complexes at concentrations higher than 1:8 were almost incapable of responding in MLC. ALG–Chlor complexes were also highly inhibitory.