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Unresponsiveness of Intrahepatic Lymphocytes to Bacterial Superantigen: Rapid Development of Suppressive Mac‐1 high Cells in the Mouse Liver
Author(s) -
Terabe Masaki,
Shimizu Masumi,
Mabuchi Ayako,
Matui So,
Morikawa Hiroyasu,
Kaneda Kenji,
Kakiuchi Terutaka,
Yokomuro Kozo
Publication year - 2000
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2000.9875
Subject(s) - cd40 , flow cytometry , population , spleen , antigen presenting cell , cd11c , immunology , microbiology and biotechnology , clone (java method) , macrophage , t lymphocyte , antigen , t cell , biology , chemistry , cytotoxic t cell , immune system , medicine , in vitro , dna , biochemistry , genetics , environmental health , gene , phenotype
Abstract We previously found that a small dose (2 μg per mouse) of staphylococcal enterotoxin B (SEB) induced early emerging unresponsiveness in intrahepatic‐lymphocyte populations (IHLs). The purpose of this study was to reveal the inducing role of accessory cells involved in IHLs in this phenomenon. IHLs prepared at 3 to 24 hours after SEB injection failed to proliferate in response not only to SEB but also to SEA, representing ligand‐nonspecific unresponsiveness, whereas spleen cells (SPCs) and mesenteric lymph‐node cells showed transient proliferation. Unresponsiveness in IHLs was related to a deficit of their accessory cell function as measured by coculture of irradiated IHLs and antigen‐specific, type 1 T‐helper (Th1) clone cells. High levels of nitrite were detected in the culture supernatant. Supplement of N G ‐monomethyl‐ l ‐arginine lowered nitrite levels and concurrently restored the proliferative response of Th1 cells, indicating the involvement of nitric oxide in suppression. Adherent cells prepared from IHLs well reproduced these results. As shown by flow cytometry, Mac‐1 high Ia + cells, which mainly included F4/80 + cells (macrophages) and a minor population of CD11c + cells (dendritic cells), increased in proportion in IHLs but not in SPCs at 6 to 24 hours. Depletion of Mac‐1 high cells from IHLs with antibody‐coated magnetic beads recovered the proliferative response. Depleted Mac‐1 high cells had a monocytoid appearance. In immunostained sections, Kupffer cells came to highly express both Mac‐1 and Ia at 12 hours. These results indicate that Mac‐1 high Ia + adherent cells, largely Kupffer cells activated by SEB, nonspecifically suppress the proliferation of Th1 cells via nitric oxide production before manifestation of ligand‐specific unresponsiveness.