title: Potent costimulation of effector T lymphocytes by human collagen type I.
abstract: Purified, resting peripheral blood T lymphocytes were previously reported to undergo beta(1) integrin-dependent activation when cultured with anti-CD3 mAb coimmobilized with fibronectin, but not type I collagen. However, the extravascular T cells that encounter immobilized extracellular matrix proteins and are involved in disease pathogenesis have different properties from resting peripheral blood cells. In this study, we confirm that resting CD4(+) and CD8(+) T cells from peripheral blood are costimulated by immobilized fibronectin, but not type I collagen. In contrast, Ag- or mitogen-stimulated CD4(+) and CD8(+) T cell lines, used as models of the effector cells involved in disease, are more potently costimulated by type I collagen than fibronectin. The collagen-induced effects are similar in assays with serum-free medium and in more physiological assays in which anti-CD3 mAb is replaced by a threshold concentration of Ag and irradiated autologous PBMC as APC. The responses are beta(1) integrin dependent and mediated largely by very late Ag (VLA) 1 and 2, as shown by their up-regulation on the T cell lines as compared with freshly purified resting PBL, and by the effects of blocking mAb. Reversed phase HPLC located the major costimulatory sequence(s) in the alpha1 chain of type I collagen, the structure of which was confirmed by amino acid sequencing. The results demonstrate the potential importance of type I collagen, an abundant extracellular matrix protein, in enhancing the activation of extravascular effector T cells in inflammatory disease, and point to a new immunotherapeutic target.
authors.affiliation: Division of Dermatology, University of Leicester, Leicester, United Kingdom.
authors.forename: W H
authors.initials: WH
authors.lastname: Rao
authors.forename: J M
authors.initials: JM
authors.lastname: Hales
authors.forename: R D
authors.initials: RD
authors.lastname: Camp
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D002469:Cell Separation; D003094:Collagen / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism / Q000502:physiology; D006801:Humans; D039423:Integrin alpha1; D039421:Integrin alpha2; D039422:Integrin alpha3; D016023:Integrins / Q000096:biosynthesis / Q000502:physiology; D007399:Interphase / Q000276:immunology; D008213:Lymphocyte Activation / Q000502:physiology*; D016853:Muromonab-CD3 / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000502:physiology*
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D039423:Integrin alpha1; D039421:Integrin alpha2; D039422:Integrin alpha3; D016023:Integrins; D016853:Muromonab-CD3; D003094:Collagen