Adhesion molecules in human islet β-cells : de novo induction of ICAM-1 but not LFA-3

• Published in: Diabetes (New York, N.Y.) Vol. 40; no. 11; pp. 1382 - 1390
• Main Authors: VIVES, M, SOLDEVILA, G, ALCALDE, L, LORENZO, C, SOMOZA, N, PUJOL-BORRELL, R
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01-11-1991
• Subjects: Antigens, Surface - genetics; Antigens, Surface - physiology; Biological and medical sciences; CD58 Antigens; Cell Adhesion Molecules - analysis; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - physiology; Cell Transformation, Viral - genetics; Cell Transformation, Viral - physiology; Cells, Cultured; Diabetes. Impaired glucose tolerance; Dose-Response Relationship, Drug; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fluorescent Antibody Technique; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; HLA Antigens - genetics; HLA Antigens - physiology; Humans; Intercellular Adhesion Molecule-1; Interferon-gamma - pharmacology; Interleukin-1 - pharmacology; Interleukin-6 - pharmacology; Islets of Langerhans - chemistry; Islets of Langerhans - cytology; Islets of Langerhans - physiology; Medical sciences; Membrane Glycoproteins - genetics; Membrane Glycoproteins - physiology; Simian virus 40 - physiology; Tumor Necrosis Factor-alpha - pharmacology; Endocrinopathy; Human; B-Cell; Pathogenesis; Langerhans islet; T-Lymphocyte; Cell adhesion molecule; Insulin dependent diabetes; Adhesion
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diab.40.11.1382

Understanding how T lymphocytes recognize beta-cell autoantigens is essential for the elucidation of the pathogenesis of insulin-dependent diabetes mellitus. The increased and ectopic expression of HLA class I and II molecules detected in human beta-cells may facilitate this interaction. T-lymphocyte recognition of surface antigens also involves adhesion accessory molecules: intercellular adhesion molecule 1 (ICAM-1) and lymphocyte function-associated antigen 3 (LFA-3). These molecules not only allow cell contact but can also provide costimulatory signals for T-lymphocyte activation. Levels of ICAM-1 and LFA-3 expression in normal human islet cells and regulation of their expression by cytokines interferon-gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), and IL-6 have been studied by two-color immunofluorescence staining of pancreatic cryostat sections and fluorescence-activated cell sorter analysis. Neither ICAM-1 nor LFA-3 could be demonstrated in sections or in fresh cell preparations, but after 18 h of culture, beta-, alpha-, and delta-cells expressed spontaneously moderate levels of ICAM-1 (but not LFA-3). IFN-gamma and TNF-alpha alone or in combination strongly enhanced this spontaneous expression of ICAM-1 in a time- and/or dose-dependent and additive manner but had no effect on LFA-3. An SV40-transformed islet cell line showed high basal levels of both ICAM-1 and LFA-3, but the response to cytokines followed the same pattern as primary cultures.