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 activated antigen-presenting cells (APC). In the present study, we examined in vitro effects of immunotoxins (ITs) composed of gelonin conjugated to mAbs against CD80 or CD86 (alphaCD80-IT and alphaCD86-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 alphaCD86-IT (72%) and alphaCD80-IT (30%) was significantly higher than alphaCD86 (54%) and alphaCD80 (11%). In reculture MLC experiments it was found that peripheral blood mononuclear cells pretreated with alphaCD86/alphaCD80 regained full stimulatory capacity whereas alphaCD86-IT/alphaCD80-IT pretreatment induced >95% loss of stimulatory capacity. Our results therefore demonstrate that these alphaB7-ITs functionally block B7-CD28 costimulatory signaling and eliminate activated APC.
Otten
H G
HG
Department of Medical Immunology, Jordan Laboratory, University Hospital Utrecht, The Netherlands. h.g.otten@lab.azu.nl
Vooijs
W C
WC
van der Gouw
L
L
de Boer
M
M
de Gast
G C
GC
D000937:Antigen-Antibody Reactions; D000938:Antigen-Presenting Cells / Q000378:metabolism; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D051940:B7-2 Antigen; D002478:Cells, Cultured; D003851:Deoxyribonucleases / Q000494:pharmacology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects* / Q000276:immunology; D000922:Immunotoxins / Q000276:immunology / Q000494:pharmacology*; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D010940:Plant Proteins / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D054789:Ribosome Inactivating Proteins, Type 1; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D000922:Immunotoxins; D008562:Membrane Glycoproteins; D010940:Plant Proteins; D011500:Protein Synthesis Inhibitors; D054789:Ribosome Inactivating Proteins, Type 1; C025674:GEL protein, Gelonium multiflorum; D003851:Deoxyribonucleases