title: [Cellular immune dysfunction in the NOD mouse: suppression of concanavalin A-induced responses in spleen cells by activated macrophages].
abstract: It is generally accepted that T lymphocyte-mediated autoimmunity contributes to the pathogenesis of Type 1 diabetes in humans and animals. Using spleen cells from nonobese diabetic (NOD) mice, a model of human Type 1 diabetes, we have analyzed the subset of T lymphocytes by flow cytometry and investigated concanavalin A (Con A)-induced interleukin 2 (IL-2) production and cell proliferation. NOD mice showed a higher percentage of Thy1.2+, L3T4+, and Lyt2+ T lymphocytes than did control ICR mice through the whole age examined. Spleen cells from a large majority of NOD mice were found to generate very low IL-2 production and cell proliferation in response to Con A. However, a few mice preserved their responsiveness to Con A. The following reasons may indicate that macrophage-mediated suppression participates in the deficient function of NOD spleen cells. (a) Macrophage depletion from NOD spleen cells retrieved Con A-induced IL-2 production. (b) Thioglycollate-induced peritoneal exudate cells containing many activated macrophages could completely suppress cell proliferation. (c) Prostaglandin synthetase inhibitor indomethacin reversed the suppression of IL-2 production by macrophages. (d) Conversely, exogenous prostaglandins could show the partial suppression of IL-2 production. These results suggest that activated macrophages suppress the response of NOD spleen cells to Con A mostly through prostaglandins. This impairment may contribute to the pathogenesis of Type 1 diabetes in NOD mice.
authors.affiliation: Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kawase
authors.forename: K
authors.initials: K
authors.lastname: Yokono
authors.forename: M
authors.initials: M
authors.lastname: Nagata
authors.forename: N
authors.initials: N
authors.lastname: Hatamori
authors.forename: H
authors.initials: H
authors.lastname: Akiyama
authors.forename: T
authors.initials: T
authors.lastname: Sakamoto
authors.forename: K
authors.initials: K
authors.lastname: Yonezawa
authors.forename: S
authors.initials: S
authors.lastname: Yaso
authors.forename: K
authors.initials: K
authors.lastname: Shii
authors.forename: S
authors.initials: S
authors.lastname: Baba
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D007111:Immunity, Cellular; D007165:Immunosuppression Therapy; D007213:Indomethacin / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis; D007958:Leukocyte Count; D008262:Macrophage Activation; D051379:Mice; D008815:Mice, Inbred Strains; D011453:Prostaglandins / Q000378:metabolism / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D007376:Interleukin-2; D011453:Prostaglandins; D003208:Concanavalin A; D007213:Indomethacin