THE EFFECT OF IMMUNOTOXINS DIRECTED AGAINST CD80 AND CD86 ON PRIMARY T-CELL ALLORESPONSES

Activation of primary resting T cells requires costimulation which can be delivered by the B7 molecules (CD80 and CD86) expressed on activat ed antigen-presenting cells (APC). In the present study, we examined i n vitro effects of immunotoxins (ITs) composed of gelonin conjugated t o mAbs against CD80 or CD86 (alpha CD80-IT and alpha CD86-IT). The spe cificity of both ITs was demonstrated using CD80 and CD86 transfected cell lines. In primary mixed lymphocyte cultures (MLCs), it was found that the average inhibitory capacity of alpha CD86-IT (72%) and alpha D80-IT (30%) was significantly higher than alpha CD86 (54%) and alpha CD80 (11%). In reculture MLC experiments it was found that peripheral blood mononuclear cells pretreated with alpha CD86/alpha CD80 regained full stimulatory capacity whereas alpha CD86-IT/alpha CD80-IT pretrea tment induced >95% loss of stimulatory capacity. Our results therefore demonstrate that these alpha B7-ITs functionally block B7-CD28 costim ulatory signaling and eliminate activated APC.