title: Costimulation via CD55 on human CD4+ T cells mediated by CD97.
abstract: Decay-accelerating factor (CD55) is a complement regulatory protein, which is expressed by most cells to protect them from complement-mediated attack. CD55 also binds CD97, an EGF-TM7 receptor constitutively expressed on granulocytes and monocytes and rapidly up-regulated on T and B cells upon activation. Early results suggested that CD55 could further enhance T cell proliferation induced by phorbol ester treatment. The present study demonstrates that coengagement of CD55, using either cross-linking mAbs or its natural ligand CD97, and CD3 results in enhanced proliferation of human peripheral blood CD4(+) T cells, expression of the activation markers CD69 and CD25, and secretion of IL-10 and GM-CSF. Recently, an increase in T cell responsiveness in CD55(-/-) mice was shown to be mediated by a lack of complement regulation. In this study, we show that direct stimulation of CD55 on CD4(+) T cells with CD97 can modulate T cell activation but does not interfere with CD55-mediated complement regulation. Our results support a multifaceted role for CD55 in human T cell activation, constituting a further link between innate and adaptive immunity.
authors.affiliation: Academic Department of Clinical Oncology, Institute of Infection, Immunity and Inflammation, University of Nottingham, City Hospital, Nottingham NG5 1PB, United Kingdom.
authors.forename: Melania
authors.initials: M
authors.lastname: Capasso
authors.forename: Lindy G
authors.initials: LG
authors.lastname: Durrant
authors.forename: Martin
authors.initials: M
authors.lastname: Stacey
authors.forename: Siamon
authors.initials: S
authors.lastname: Gordon
authors.forename: Judith
authors.initials: J
authors.lastname: Ramage
authors.forename: Ian
authors.initials: I
authors.lastname: Spendlove
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000502:physiology; D015703:Antigens, CD / Q000097:blood / Q000502:physiology*; D015415:Biomarkers / Q000097:blood; D017252:CD3 Complex / Q000097:blood / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018958:CD55 Antigens / Q000097:blood / Q000276:immunology / Q000502:physiology*; D049109:Cell Proliferation; D002999:Clone Cells; D003165:Complement System Proteins / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000097:blood / Q000502:physiology*; D008969:Molecular Sequence Data; D016853:Muromonab-CD3 / Q000502:physiology; D043562:Receptors, G-Protein-Coupled; D016192:Resting Phase, Cell Cycle / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: C095004:ADGRE5 protein, human; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015415:Biomarkers; D017252:CD3 Complex; D018958:CD55 Antigens; D003432:Cross-Linking Reagents; D016207:Cytokines; D008562:Membrane Glycoproteins; D016853:Muromonab-CD3; D043562:Receptors, G-Protein-Coupled; D003165:Complement System Proteins