Soluble forms of intercellular adhesion molecule-1 in insulin-dependent diabetes mellitus.
Soluble adhesion molecules are detectable at low levels in healthy people but are increased in various disorders. However, their physiological role is unknown. Circulating intercellular adhesion molecule-1 (cICAM-1) may modulate inflammation or arise as a consequence of inflammation. We have described elevated concentrations of cICAM-1 in subjects at risk of developing insulin-dependent diabetes mellitus (IDDM), compared with recent-onset IDDM patients and healthy controls. Here we tested the ability of a monomeric soluble recombinant form of ICAM-1 (rICAM-1), to prevent the proliferation of T cells to islet-cell and other antigens. We also tested the ability of two multivalent ICAM-1-immunoglobulin (ICAM-1-Ig) fusion proteins to stop proliferation of T cells in vitro. Autoreactive T-cell proliferation was suppressed by monoclonal antibodies directed against ICAM-1 or lymphocyte-function antigen-1 (LFA-1). Furthermore, 100 mumol rICAM-1 blocked T-cell proliferation in response to an islet-cell autoantigen, and multivalent ICAM-1-Ig fusion proteins were approximately 1,000-fold more effective. The usual interleukin-2-induced proliferation of T cells was unaffected by ICAM or ICAM-Ig. In addition, rICAM-1 blocked primary T-cell responses from peripheral blood mononuclear cells of newly diagnosed IDDM patients in concentrations similar to elevated cICAM-1 concentrations in individuals at risk for the disease. Thus, naturally circulating ICAM-1 may downregulate inflammation in subjects at risk of developing IDDM. Ig-ICAM-1 fusion proteins may thus provide novel means to intervene in the pathogenesis of autoimmune diseases.
Roep
B O
BO
Department of Immunohaematology, University Hospital, Leiden, Netherlands.
Heidenthal
E
E
de Vries
R R
RR
Kolb
H
H
Martin
S
S
D001324:Autoantigens / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000097:blood / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1; D007376:Interleukin-2 / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology
D001324:Autoantigens; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1