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

H. G. Otten*, W. C. Vooijs, L. Van Der Gouw, M. De Boer, G. C. De Gast

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

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 examined in vitro effects 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.

Original languageEnglish
Pages (from-to)270-274
Number of pages5
JournalTissue Antigens
Volume52
Issue number3
Publication statusPublished - 5 Oct 1998

Keywords

  • CD80
  • CD86
  • Human
  • Immunotoxin

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