Fc receptor binding of anti-CD3 monoclonal antibodies is not essential for immunosuppression, but triggers cytokine-related side effects

A.C.T.M. Vossen, G.J.M. Tibbe, M.J. Kroos, J.G.J. van de Winkel, R. Benner, H.F.J. Savelkoul

Research output: Contribution to journalArticleAcademicpeer-review

42 Citations (Scopus)

Abstract

A major drawback to the use of OKT3, a mouse anti-CD3 monoclonal antibody (mAb), as an immunosuppressive agent is the associated cytokine release syndrome. We used a mouse model to elucidate the properties of anti-CD3 mAb responsible for these cytokine-related side effects. We have previously demonstrated that the hamster anti-CD3 mAb 145-2C11 induced strong cytokine release and morbidity in vivo, whereas two rat anti-CD3 mAb 17A2 and KT3 did not. In the current study, we show that the mitogenic capacity of soluble anti-CD3 mAb in vitro correlates with their induction of side effects in vivo. Mitogenesis in vitro and tumor necrosis factor-alpha (TNF-alpha) release in vivo induced by anti-CD3 mAb could be inhibited by the anti-Fc gamma R mAb 2.4G2, indicating that Fc gamma R binding of anti-CD3 mAb is responsible for their mitogenic properties and for their induction of side effects. Importantly, the two non-mitogenic rat anti-CD3 mAb were equally capable of suppressing skin allograft rejection as the mitogenic hamster anti-CD3 mAb, suggesting Fc gamma R binding of anti-CD3 mAb is not essential for their immunosuppressive properties. This suggestion is reinforced by our demonstration that administration of 2.4G2 in vivo did not interfere with immunosuppression of skin allograft rejection by 145-2C11. These findings suggest that clinical use of non-mitogenic anti-CD3 mAb will result in effective immunosuppression without cytokine-related side effects.
Original languageEnglish
Pages (from-to)1492-1496
JournalEuropean journal of immunology
Volume25
Issue number6
DOIs
Publication statusPublished - 1995
Externally publishedYes

Keywords

  • Anti‐CD3 monoclonal antibodies
  • CD3
  • Immunosuppression
  • Side effects

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