Adhesion molecules in human islet beta-cells. De novo induction of ICAM-1 but not LFA-3.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Vives
M
M
Immunology Lab, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Spain.
Soldevila
G
G
Alcalde
L
L
Lorenzo
C
C
Somoza
N
N
Pujol-Borrell
R
R
D000954:Antigens, Surface / Q000235:genetics* / Q000502:physiology; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000235:genetics* / Q000502:physiology; D002472:Cell Transformation, Viral / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006680:HLA Antigens / Q000235:genetics / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007515:Islets of Langerhans / Q000737:chemistry* / Q000166:cytology / Q000502:physiology; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology; D013539:Simian virus 40 / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000954:Antigens, Surface; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules; D006680:HLA Antigens; D007375:Interleukin-1; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma