Lymphokines, substances elaborated by antigenically- or mitogenically-stimulated lymphocytes, play a crucial part in the manifestation of cellular immunity. These include human migration inhibitory factor (MIF), a lymphokine which inhibits the migration of macrophages out of capillary tubes. The proposed study has been designed to investigate the antigen-specific induction of synthesis and the cellular origin of the different species of human MIF and the significance of distinct MIF species in the biological situation. Studies have shown that human MIF produced by concanavalin A stimulated peripheral blood mononuclear cells is heterogeneous, consisting of at least three distinct molecular species. Furthermore, different antigens induce the production of distinct MIF species.
The aims of this proposal are, therefore, to analyze the conditions for the production of the different MIF species using various antigens, B cell- and T-cell mitogens. To examine the biological significance of antigen-dependent polymorphism of MIF species, we propose to investigate whether different MIF species induced by different antigens are associated with distinct capacities to enhance destruction or inhibit growth of fungi or of viruses by macrophages. We are also interested in the identification of the cellular origin of different MIF species using highly purified lymphocyte subpopulations and monoclonal anti T cell subset antibodies. In order to increase the amount of MIF species produced, human lymphoid cell lines, hybridomas and T cell clones propagated by Interleucin 2 will be screened for MIF production. Attempts will be made to raise monoclonal antibodies against distinct MIF species when large quantities of each species become available. In addition, studies will be carried out to determine whether Lambda-interferon in MIF-containing lymphocyte supernatants is also heterogeneous in order to obtain more information on lymphokine heterogeneity in general. This knowledge should be useful for clarification of the action of lymphokines, permitting the eventual manipulation of these events in clinical situations.
