1304 Mediator Production

When lymphocytes obtained from persons or animals exhibiting delayed hypersensitivity are stimulated in vitro by specific antigen, they produce a number of soluble substances with various biologic activities including migration inhibitory factor (MIF) 1 and lymphocyte mitogenic factor (LMF) (1-4). Since delayed hypersensitivity reactions have been generally assumed to be mediated by thymus-dependent (T) lymphocytes, it has been further assumed that antigeninduced production of MIF was by T lymphocytes and thus its presence or absence reflected T-cell function. The correlation of macrophage migration inhibition with delayed hypersensitivity and not with antibody production (2, 5, 6), the production of MIF by lymphocytes from patients with sex-linked agammaglobulinemia but not thymic aplasia (7), and the lack of MIF production in numerous immunodeficiency diseases linked with depressed delayed hypersensitivity and normal antibody production (8, 9) are part of the foundation for this conclusion. The availability of a new method of cell separation utilizing affinity column chromatography which allows the quantitative recovery of virtually pure populations of human T and B lymphocytes has permitted a re-evaluation of the functional properties of T and B cells (10, 11). Using this technique, Chess et al. have recently shown that both T and B human blood lymphocytes respond to mitogens such as phytohemagglutinin (PHA), concanavalin A, and pokeweed, but only T-cell populations proliferate in response to specific soluble or cell surface antigens (10, 11). In the present study, we have used this affinity column separation technique to critically evaluate the hypothesis that antigen-induced mediator production is the exclusive property of T lymphocytes. Highly purified Tand B-lymphocyte populations were stimulated by specific antigen and their ability to produce two