The effect of immunotoxins directed against CD80 and CD86 on primary T‐cell alloresponses

Abstract:Activation of primary resting T cells requires costimulation which can be delivered by the B7 molecules (CD80 and CD86) expressed on activated antigen‐presenting cells (APC). In the present study, we examinedin vitroeffects of immunotoxins (ITs) composed of gelonin conjugated to mAbs against CD80 or CD86 (αCD80‐IT and αCD86‐IT). The specificity 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 αCD86‐IT (72%) and αCD80‐IT (30%) was significantly higher than αCD86 (54%) and αCD80 (11%). In reculture MLC experiments it was found that peripheral blood mononuclear cells pretreated with αCD86/αCD80 regained full stimulatory capacity whereas αCD86‐IT/ αCD80‐IT pretreatment induced >95% loss of stimulatory capacity. Our results therefore demonstrate that these αB7‐ITs functionally block B7‐CD28 costimulatory signaling and eliminate activated APC.