title: The soluble form of CTLA-4 from serum of patients with autoimmune diseases regulates T-cell responses.
abstract: Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) is a costimulatory receptor transducing a potent inhibitory signal. Increasing evidence showed that CTLA-4 gene is an important susceptibility locus for autoimmune disorders. Alternatively spliced mRNA generates a soluble form, called sCTLA-4. Whereas low levels of sCTLA-4 are detected in normal human serum, increased/high serum levels are observed in several autoimmune diseases. The biological significance of increased sCTLA-4 serum level is not fully clarified yet. It can be envisaged that sCTLA-4 specifically inhibits the early T-cell activation by blocking the interaction of CD80/CD86 with the costimulatory receptor CD28. On the other hand, higher levels of sCTLA-4 could contend the binding of the membrane form of CTLA-4 with CD80/CD86, in later activation phase, causing a reduction of inhibitory signalling. We showed that sCTLA-4 from sera of patients with different autoimmune diseases is able to display functional activities on an in vitro system acting on the proliferation capability and modulating the secretion of cytokines. We observed a dual effect of sCTLA-4: inhibiting the secretion of IFN-γ , IL-2, IL-7, and IL-13 and activating the secretion of TGF-β and IL-10. This study underlines the role of sCTLA-4 in modulating the immune response and its relevance in autoimmune disease pathogenesis.
authors.affiliation: Section of Human Anatomy, Department of Experimental Medicine, University of Genoa, Via De Toni 14, 16132 Genoa, Italy ; Departments of Medicine and Cell Biology, North Shore University Hospital, Manhasset, NY 11030, USA.
authors.forename: Rita
authors.identifier: 0000-0002-0174-6133
authors.initials: R
authors.lastname: Simone
authors.affiliation: Autoimmunity Unit, Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy.
authors.forename: Giampaola
authors.initials: G
authors.lastname: Pesce
authors.affiliation: Autoimmunity Unit, Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy.
authors.forename: Princey
authors.initials: P
authors.lastname: Antola
authors.affiliation: Autoimmunity Unit, Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy.
authors.forename: Margarita
authors.initials: M
authors.lastname: Rumbullaku
authors.affiliation: Autoimmunity Unit, Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Bagnasco
authors.affiliation: Laboratory of Clinical Pathology, San Antonio Hospital, Tolmezzo, 33100 Udine, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Bizzaro
authors.affiliation: Section of Human Anatomy, Department of Experimental Medicine, University of Genoa, Via De Toni 14, 16132 Genoa, Italy.
authors.forename: Daniele
authors.identifier: 0000-0002-1623-1116
authors.initials: D
authors.lastname: Saverino
mesh_terms: D001327:Autoimmune Diseases / Q000097:blood* / Q000276:immunology*; D060908:CTLA-4 Antigen / Q000097:blood*; D049109:Cell Proliferation; D006801:Humans; D056747:Immunomodulation; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D012995:Solubility; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014019:Tissue Donors; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D060908:CTLA-4 Antigen; D018793:Interleukin-13; D007376:Interleukin-2; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma