title: Glial cells as suppressor cells: characterization of the inhibitory function.
abstract: Rat retinal glial cells (Müller cells) profoundly suppress antigen-driven activation, as well as the subsequent interleukin-2 (IL-2)-dependent expansion of autoimmune and conventional-immune syngeneic T-helper lymphocytes, through a contact-dependent mechanism. Characterization of this inhibitory function showed that some activation parameters of autoimmune T-helper lymphocytes specific to the retinal soluble antigen, responding to antigen presented on syngeneic antigen-presenting cells, were differentially affected by coculture with Müller cells. In contrast to endogenous IL-2 production, IL-2-receptor generation and proliferation, the production of interleukin-3 and of interferon-gamma were not inhibited. Inhibition of IL-2-supported proliferation of cells which had already generated the IL-2 receptor was markedly potentiated in the presence of the specific antigen, in a dose-dependent manner. The extent of inhibition was proportional to the number of Müller cells in the culture. The suppression appeared not to involve a major histocompatibility complex (MHC) Class II-related interaction and could act across allogeneic and even xenogeneic barriers. Inhibition affected normal lymphocytes, including primed T cells responding to antigen or to IL-2, unprimed spleen cells responding to the T-cell mitogen concanavalin A (Con-A) and, to a lesser extent, unprimed spleen cells responding to the B-cell mitogen bacterial lipopolysaccharide (LPS). Several permanently transformed cell lines of mouse, rat and human origin were not affected. These results may suggest participation of organ-resident cells in regulation of locally occurring immune processes.
authors.affiliation: Laboratory of Immunology, NIH, Bethesda, MD 20892.
authors.forename: R R
authors.initials: RR
authors.lastname: Caspi
authors.forename: F G
authors.initials: FG
authors.lastname: Roberge
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D002450:Cell Communication; D002478:Cells, Cultured; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000096:biosynthesis; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D009457:Neuroglia / Q000276:immunology / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D012160:Retina / Q000166:cytology / Q000276:immunology; D013045:Species Specificity; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014605:Uveitis / Q000276:immunology / Q000473:pathology
chemical_list: D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D008222:Lymphokines; D008934:Mitogens; D015375:Receptors, Interleukin-2