Simultaneous activation of natural killer T cells and autoantibody production in mice injected with denatured syngeneic liver tissue

• Published in: Clinical and experimental immunology 2002-09, Vol.129 (3), p.397-404
• Main Authors: NAITO, T., KAWAMURA, T., BANNAI, M., KOSAKA, T., KAMEYAMA, H., SHIMAMURA, K., HOSHI, O., USHIKI, T., HATAKEYAMA, K., ABO, T.
• Format: Article
• Language: English
• Subjects: Animal Studies; Animals; Antigens - analysis; Antigens, Ly; Antigens, Surface; Autoantibodies - blood; autoantibody production; Autoantigens - administration & dosage; Autoantigens - chemistry; Autoantigens - immunology; Autoimmune Diseases - immunology; Autoimmune Diseases - pathology; autoreactive T cells; B-Lymphocytes - immunology; Biological and medical sciences; CD1dhigh B cells; CD3 Complex - analysis; Cells, Cultured; denatured liver tissue; Female; General aspects; Immunopathology; Injections, Intraperitoneal; Killer Cells, Natural - immunology; Kinetics; Lectins, C-Type; Liver - immunology; Liver - pathology; Liver - ultrastructure; Lymphocyte Activation; Lymphocyte Count; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Inbred MRL lpr; natural killer T cells; NK Cell Lectin-Like Receptor Subfamily B; Protein Denaturation; Proteins - analysis; Transaminases - blood
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.2002.01910.x

SUMMARY Denatured syngeneic liver tissue prepared by mechanical procedures was intraperitoneally injected into adult C57BL/6 mice. In parallel with a decrease in the total number of lymphocytes in the liver, spleen, and thymus from days 1–7 after the injection, the proportion of the CD4+NK1·1+CD3int subset of these cells (i.e. natural killer T or NKT cells) increased in the liver. Even the absolute number of these NKT cells increased in the liver on days 14 and 21. In response to the injection of denatured liver tissue, tissue damage was induced in the liver, as shown by elevated levels of serum transaminases and hepatocyte degeneration observed by electron microscopy. Sera obtained on days 7 and 14 contained autoantibodies including anti‐DNA antibodies. The proportion of CD1dhighB cells in the liver was found to decrease on days 1–7. In other words, denatured liver tissue stimulated both NKT cells and certain B cells in the liver. These results suggest that liver lymphocytes might contain not only autoreactive T cells (e.g. CD3int or NKT cells) but also some B cells (e.g. B‐1 cells) which produce autoantibodies and that the denatured tissue had the potential to stimulate these lymphocytes and to evoke an autoimmune‐like state.