Human memory T cell activation: Effects of monoclonal antibodies directed at interleukin-2, receptors for interleukin-2, or interferon-γ

Manikkam Suthanthiran, Kurt H. Stenzel

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2 Citations (Scopus)

Abstract

Several polyclonal T cell activators can induce the differentiation of quiescent antigen-specific memory T cells (memory cells) into specific secondary cytotoxic T cells, in the absence of the original priming alloantigens. Such activation represents a potential pathway by which immunologically nonspecific signals can elicit specific antiallograft immunity. We therefore investigated the molecular basis for antigen-independent activation of memory cells using as probes recombinant interleukin-2 and monoclonal antibodies directed at IL- 2, IL-2 receptors (IL-2R), or interferon-7 (IFN-γ). An- tigen-specific memory cells, generated in human long- term-primary mixed lymphocyte cultures, were induced to proliferate, exhibit antigen specific secondary cytolytic activity, or produce IFN-γ by recombinant DNA human IL-2 produced in E Coli. Monoclonal antibodies directed at the IL-2R or at IL-2 inhibited IL-2-mediated proliferation, cytolytic activity, or production of IFN-γ- Monoclonal antibodies directed at IFN-γ did not inhibit alloantigen or IL-2 mediated activation of memory cells. Our findings suggest that successful interaction between IL-2 and its receptor expressed on memory cells represents a plausible pathway by which an immunologically nonspecific signal might elicit specific antiallograft immunity. Moreover, therapeutic strategies that include antibodies directed at the IL-2 and/or IL-2R and not antibodies directed at IFN-γ will inhibit IL-2-dependent alloimmunity.

Original languageEnglish
Pages (from-to)292-298
Number of pages7
JournalTransplantation
Volume46
Issue number2
Publication statusPublished - 1 Jan 1988
Externally publishedYes

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ASJC Scopus subject areas

  • Transplantation
  • Immunology

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