title: A positively selecting thymic epithelial cell line lacks costimulatory activity.
abstract: The participation of costimulatory molecule interactions in positive selection of T lymphocytes was addressed by assessing the ability of a positively selecting thymic epithelial cell (TEC) line, 427.1, to stimulate allospecific CTL responses. Stimulation of H-2s spleen cells with the H-2b expressing 427.1 line does not result in the generation of cells capable of lysing H-2b target cell lines. The level of expression of MHC class I molecules by 427.1 is lower than that found in other stimulatory TEC lines. However, this finding does not account for the nonstimulatory phenotype. Up-regulation of MHC class I did not result in stimulation, and fusion of 427.1 cells with stimulatory TEC resulted in a line with low MHC class I molecule expression and stimulatory phenotype. The TEC line 427.1 does not express the costimulatory molecule B7/BB1, and transfection of the B7/BB1-encoding DNA results in expression of the molecule and conversion into a stimulatory phenotype, demonstrating directly that the non-stimulatory phenotype is a result of lack of costimulation. However, B7/BB1 expression does not improve the ability of 427.1 TECs to induce positive selection. Intrathymic injection of the B7/BB1 transfected, compared with mock transfected 427.1 cells, rescued fewer CD8+ mature thymocytes in beta 2-microglobulin negative mice. Therefore, unlike the peripheral T cell responses to Ag, positive selection of T cells in the thymus may not depend on the costimulation provided by the presenting cell.
authors.affiliation: Department of Immunology, University of Washington, Seattle 98195.
authors.forename: S
authors.initials: S
authors.lastname: Vukmanović
authors.forename: G
authors.initials: G
authors.lastname: Stella
authors.forename: P D
authors.initials: PD
authors.lastname: King
authors.forename: R
authors.initials: R
authors.lastname: Dyall
authors.forename: K A
authors.initials: KA
authors.lastname: Hogquist
authors.forename: J T
authors.initials: JT
authors.lastname: Harty
authors.forename: J
authors.initials: J
authors.lastname: Nikolić-Zugić
authors.forename: M J
authors.initials: MJ
authors.lastname: Bevan
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D001483:Base Sequence; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D017931:DNA Primers / Q000737:chemistry; D004847:Epithelial Cells; D006183:H-2 Antigens / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology*
chemical_list: D018122:B7-1 Antigen; D017931:DNA Primers; D006183:H-2 Antigens