Mechanisms of Mycobacterium avium‐induced resistance against insulin‐dependent diabetes mellitus (IDDM) in non‐obese diabetic (NOD) mice: role of Fas and Th1 cells

• Published in: Clinical and experimental immunology Vol. 115; no. 2; pp. 248 - 254
• Main Authors: MARTINS, T. C., ÁGUAS, A. P.
• Format: Journal Article
• Language: English
• Published: Oxford BSL Blackwell Science Ltd 01-02-1999; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: AIDS/HIV; Animals; Antigens, CD - biosynthesis; Antigens, Differentiation, T-Lymphocyte - biosynthesis; apoptosis; Biological and medical sciences; Clonal Anergy; Clonal Deletion; cytotoxicity; Cytotoxicity, Immunologic; diabetes; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - prevention & control; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fas Ligand Protein; fas Receptor - immunology; Interferon-gamma - biosynthesis; Interleukin-4 - biosynthesis; Lectins, C-Type; Medical sciences; Membrane Glycoproteins - immunology; Mice; Mice, Inbred NOD; Models, Immunological; Mycobacterium avium; Mycobacterium avium - immunology; Original; Th1 Cells - immunology; Th1/Th2; tolerance; Tuberculosis - immunology; Endocrinopathy; Animal model; Th1 lymphocyte; Autoimmune disease; Helper cell; Cytotoxicity; Cellular immunity; Immunotherapy; T-Lymphocyte; Bacteria; Immunopathology; Immune response; NOD mouse; Rodentia; Mycobacterium avium; Vertebrata; Membrane receptor; Mammalia; Treatment; Mouse; Mycobacteriales; Animal; Mycobacteriaceae; Insulin dependent diabetes; Actinomycetes; Apoptosis
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.1999.00781.x

NOD mice spontaneously develop autoimmune diabetes. One of the manipulations that prevent diabetes in NOD mice is infection with mycobacteria or immunization of mice with mycobacteria‐containing adjuvant. Infection of NOD mice with Mycobacterium avium, done before the mice show overt diabetes, results in permanent protection of the animals from diabetes and this protective effect is associated with increased numbers of CD4+ T cells and B220+ B cells. Here, we investigate whether the M. avium‐induced protection of NOD mice from diabetes was associated with changes in the expression of Fas (CD95) and FasL by immune cells, as well as alterations in cytotoxic activity, interferon‐gamma (IFN‐γ) and IL‐4 production and activation of T cells of infected animals. Our data indicate that protection of NOD mice from diabetes is a Th1‐type response that is mediated by up‐regulation of the Fas–FasL pathway and involves an increase in the cytotoxicity of T cells. These changes are consistent with induction by the infection of regulatory T cells with the ability of triggering deletion or anergy of peripheral self‐reactive lymphocytes that cause the autoimmune disease of NOD mice.