Adhesion Molecules in Human Islet β-cells: De Novo Induction of ICAM-1 but Not LFA-3

Understanding how T lymphocytes recognize β-cell autoantigens is essential forthe elucidation of the pathogenesis of insulin-dependent diabetes mellitus. The increased and ectopic expression of HLA class I and II molecules detected in human β-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-γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), 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, β-, α-, and δ-cells expressed spontaneously moderate levels of ICAM-1 (but not LFA-3). IFN-γ and TNF-α alone or in combination strongly enhanced this spontaneous expressionof 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.Theabsence of constitutive expression of adhesion molecules in β-cells supports the concept that they are immunologically silent cells and may also explain the failure of inducing autoimmune diabetes in transgenic mice by the sole expression of class II in theβ-cells via genetic manipulation. The induction of ICAM-1 by the same cytokines that can induce HLA class I and class II expression suggests that, in the diabetic pancreas, remaining β-cells probably express ICAM-1 concomitantly with HLA products.