OKT3-associated adverse reactions: Mechanistic basis and therapeutic options

Manikkam Suthanthiran, M. Fotino, R. R. Riggio, J. S. Cheigh, K. H. Stenzel

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Abstract

OKT3, a prototypic monoclonal antibody directed at the lineage-specific CD3 antigen expressed on mature T cells, is an effective immunosuppressant in organ graft recipients. Unfortunately, a variety of adverse reactions are observed following the first and second doses of OKT3. In a series of experiments designed to examine the signaling repertoire of OKT3, it was found that (1) OKT3 is an effective substitute for the alloantigen stimulus in the activation of antigen-specific memory T cells; (2) OKT3 is a potent inducer of cytolytic activity (secondary cytotoxic T-cell activity as well as natural killer-cell activity); (3) OKT3 is also an inducer of interleukin-2 and interferon gamma production; and (4) of the immunosuppressants currently in clinical use, cyclosporine >methylprednisolone>6-mercaptopurine (an in vivo cleavage product of azathioprine) in curtailing T-cell activation with OKT3. Collectively, these observations suggest a potential mechanistic basis for the adverse reactions associated with OKT3 and provide experimental support for therapeutic strategies that include the use of cyclosporine and/or methylprednisolone before OKT3 administration.

Original languageEnglish
Pages (from-to)39-44
Number of pages6
JournalAmerican Journal of Kidney Diseases
Volume14
Issue number5 SUPPL. 2
Publication statusPublished - 1 Jan 1989
Externally publishedYes

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ASJC Scopus subject areas

  • Nephrology

Cite this

Suthanthiran, M., Fotino, M., Riggio, R. R., Cheigh, J. S., & Stenzel, K. H. (1989). OKT3-associated adverse reactions: Mechanistic basis and therapeutic options. American Journal of Kidney Diseases, 14(5 SUPPL. 2), 39-44.