title: Adhesion of immature thymocytes to thymic stromal cells through fibronectin molecules and its significance for the induction of thymocyte differentiation.
abstract: Only 10-15% of unseparated thymocytes adhered to culture plates precoated with fibronectin (FN), but 60-70% of the CD4-8- (double-negative) thymocyte population did. This population bound to FN but not to collagen, laminin, or vitronectin. Its binding to FN was inhibited by anti-FN antibody or a mixture of synthetic peptides corresponding to two different sites of FN, termed the V10 sequence and the RGDS (Arg-Gly-Asp-Ser) sequence, which interact, respectively, with the VLA-4 and VLA-5 FN receptors expressed on T-lineage cells. CD4-8- thymocytes also adhered to a monolayer of a thymic stromal cell clone, MRL104.8a, that induces growth-maintenance and differentiation of such thymocytes. The involvement of FN-FN receptor interaction in this adhesion was demonstrated by the following lines of evidence: (i) the MRL104.8a cells expressed FN molecules on their surface and (ii) the adhesion of CD4-8- thymocytes to MRL104.8a monolayers was almost completely inhibited by simultaneous addition of anti-FN antibody and a mixture of peptides (V10 plus RGDS) capable of binding to anti-FN receptors (VLA-4 and -5). Most important, blocking the adhesion of CD4-8- thymocytes to the thymic stromal cell monolayer resulted in potent inhibition of the differentiation of these thymocytes, which was otherwise induced toward the expression of CD4 and/or CD8 molecules. These results indicate that immature CD4-8- thymocytes adhere to thymic stromal cells preferentially through FN-FN receptor interaction and that such adhesion has a critical role in inducing and/or supporting the differentiation of these thymocytes.
authors.affiliation: Biomedical Research Center, Osaka University Medical School, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Utsumi
authors.forename: M
authors.initials: M
authors.lastname: Sawada
authors.forename: S
authors.initials: S
authors.lastname: Narumiya
authors.forename: J
authors.initials: J
authors.lastname: Nagamine
authors.forename: T
authors.initials: T
authors.lastname: Sakata
authors.forename: S
authors.initials: S
authors.lastname: Iwagami
authors.forename: Y
authors.initials: Y
authors.lastname: Kita
authors.forename: H
authors.initials: H
authors.lastname: Teraoka
authors.forename: H
authors.initials: H
authors.lastname: Hirano
authors.forename: M
authors.initials: M
authors.lastname: Ogata
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001665:Binding Sites; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D005353:Fibronectins / Q000737:chemistry / Q000502:physiology*; D005434:Flow Cytometry; D051379:Mice; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic / Q000378:metabolism / Q000502:physiology; D018000:Receptors, Peptide; D013950:Thymus Gland / Q000166:cytology*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; C051382:arginyl-glycyl-aspartic acid directed cell adhesion receptor