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.