Human memory T cell activation. Effects of monoclonal antibodies directed at interleukin-2, receptors for interleukin-2, or interferon-gamma.
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-gamma (IFN-gamma). Antigen-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-gamma 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-gamma. Monoclonal antibodies directed at IFN-gamma 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-gamma will inhibit IL-2-dependent alloimmunity.
D000911:Antibodies, Monoclonal / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007111:Immunity, Cellular; D007156:Immunologic Memory; D007158:Immunologic Techniques; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000502:physiology*; D007376:Interleukin-2 / Q000502:physiology*; D008213:Lymphocyte Activation; D011971:Receptors, Immunologic / Q000502:physiology*; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma