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Prevention of autoimmune diabetes with lymphotoxin in NOD mice. 1993

H Seino, and K Takahashi, and J Satoh, and X P Zhu, and M Sagara, and T Masuda, and T Nobunaga, and I Funahashi, and T Kajikawa, and T Toyota
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.

We have reported previously that chronic and systemic administration of a streptococcal preparation (OK-432), an inducer of TNF, or of recombinant hTNF prevented the development of IDDM in the two animal models of IDDM-NOD mice and BB rats. In this study, we examined the effect of LT, which is structurally and functionally related to TNF, on NOD mice with diabetes. The cumulative incidence of diabetes at 30 wk of age was 22 of 40 (55%) in nontreated female NOD mice and was 4 of 8 (50%; NS), 3 of 29 (10%; P < 0.001), and 0 of 8 (0%; P < 0.001) in female mice treated three times a week from 4 to 30 wk of age with 5, 50, or 500 U of recombinant hLT, respectively. Intensity of insulitis was slightly reduced in the long-term LT-treated mice. LT productivity by ConA-stimulated spleen cells was examined in vitro. Although no significant difference was found between NOD mice and the other mouse strains, female NOD mice were slightly but significantly (P < 0.01) lower producers of LT immunoreactivity than male NOD mice, the diabetes incidence of which is lower than that of females. The SMLR as a marker of normal immune response, which was reported to be impaired in autoimmune animals including NOD mice, was significantly lower in female than male NOD mice. However, the low SMLR in female NOD mice was significantly increased by the administration of LT, and the increase was mediated by the responder cells of the LT-treated mice.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D007959 Lymphocyte Culture Test, Mixed Measure of histocompatibility at the HL-A locus. Peripheral blood lymphocytes from two individuals are mixed together in tissue culture for several days. Lymphocytes from incompatible individuals will stimulate each other to proliferate significantly (measured by tritiated thymidine uptake) whereas those from compatible individuals will not. In the one-way MLC test, the lymphocytes from one of the individuals are inactivated (usually by treatment with MITOMYCIN or radiation) thereby allowing only the untreated remaining population of cells to proliferate in response to foreign histocompatibility antigens. Leukocyte Culture Test, Mixed,Mixed Lymphocyte Culture Test,Mixed Lymphocyte Reaction,Mixed Leukocyte Culture Test,Mixed Leukocyte Reaction,Leukocyte Reaction, Mixed,Leukocyte Reactions, Mixed,Lymphocyte Reaction, Mixed,Lymphocyte Reactions, Mixed,Mixed Leukocyte Reactions,Mixed Lymphocyte Reactions
D008233 Lymphotoxin-alpha A tumor necrosis factor family member that is released by activated LYMPHOCYTES. Soluble lymphotoxin is specific for TUMOR NECROSIS FACTOR RECEPTOR TYPE I; TUMOR NECROSIS FACTOR RECEPTOR TYPE II; and TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY, MEMBER 14. Lymphotoxin-alpha can form a membrane-bound heterodimer with LYMPHOTOXIN-BETA that has specificity for the LYMPHOTOXIN BETA RECEPTOR. TNF Superfamily, Member 1,TNF-beta,Tumor Necrosis Factor Ligand Superfamily Member 1,Tumor Necrosis Factor-beta,Lymphotoxin,Lymphotoxin-alpha3,Soluble Lymphotoxin-alpha,alpha-Lymphotoxin,Lymphotoxin alpha,Lymphotoxin alpha3,Lymphotoxin-alpha, Soluble,Soluble Lymphotoxin alpha,Tumor Necrosis Factor beta,alpha Lymphotoxin
D008297 Male Males
D003922 Diabetes Mellitus, Type 1 A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence. Diabetes Mellitus, Brittle,Diabetes Mellitus, Insulin-Dependent,Diabetes Mellitus, Juvenile-Onset,Diabetes Mellitus, Ketosis-Prone,Diabetes Mellitus, Sudden-Onset,Diabetes, Autoimmune,IDDM,Autoimmune Diabetes,Diabetes Mellitus, Insulin-Dependent, 1,Diabetes Mellitus, Type I,Insulin-Dependent Diabetes Mellitus 1,Juvenile-Onset Diabetes,Type 1 Diabetes,Type 1 Diabetes Mellitus,Brittle Diabetes Mellitus,Diabetes Mellitus, Insulin Dependent,Diabetes Mellitus, Juvenile Onset,Diabetes Mellitus, Ketosis Prone,Diabetes Mellitus, Sudden Onset,Diabetes, Juvenile-Onset,Diabetes, Type 1,Insulin Dependent Diabetes Mellitus 1,Insulin-Dependent Diabetes Mellitus,Juvenile Onset Diabetes,Juvenile-Onset Diabetes Mellitus,Ketosis-Prone Diabetes Mellitus,Sudden-Onset Diabetes Mellitus
D004797 Enzyme-Linked Immunosorbent Assay An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. ELISA,Assay, Enzyme-Linked Immunosorbent,Assays, Enzyme-Linked Immunosorbent,Enzyme Linked Immunosorbent Assay,Enzyme-Linked Immunosorbent Assays,Immunosorbent Assay, Enzyme-Linked,Immunosorbent Assays, Enzyme-Linked
D005260 Female Females
D005434 Flow Cytometry Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. Cytofluorometry, Flow,Cytometry, Flow,Flow Microfluorimetry,Fluorescence-Activated Cell Sorting,Microfluorometry, Flow,Cell Sorting, Fluorescence-Activated,Cell Sortings, Fluorescence-Activated,Cytofluorometries, Flow,Cytometries, Flow,Flow Cytofluorometries,Flow Cytofluorometry,Flow Cytometries,Flow Microfluorometries,Flow Microfluorometry,Fluorescence Activated Cell Sorting,Fluorescence-Activated Cell Sortings,Microfluorimetry, Flow,Microfluorometries, Flow,Sorting, Fluorescence-Activated Cell,Sortings, Fluorescence-Activated Cell
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012727 Sex Characteristics Those characteristics that distinguish one SEX from the other. The primary sex characteristics are the OVARIES and TESTES and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. Gender Characteristics,Gender Differences,Gender Dimorphism,Sex Differences,Sex Dimorphism,Sexual Dichromatism,Sexual Dimorphism,Characteristic, Gender,Characteristic, Sex,Dichromatism, Sexual,Dichromatisms, Sexual,Difference, Sex,Dimorphism, Gender,Dimorphism, Sex,Dimorphism, Sexual,Gender Characteristic,Gender Difference,Gender Dimorphisms,Sex Characteristic,Sex Difference,Sex Dimorphisms,Sexual Dichromatisms,Sexual Dimorphisms
D014409 Tumor Necrosis Factor-alpha Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS. Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha

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