title: Uncovering of functional alternative CTLA-4 counter-receptor in B7-deficient mice.
abstract: B7 delivers a costimulatory signal through CD28, resulting in interleukin-2 secretion and T cell proliferation. Blockade of this pathway results in T cell anergy. The in vivo role of B7 was evaluated with B7-deficient mice. These mice had a 70 percent decrease in costimulation of the response to alloantigen. Despite lacking B7 expression, activated B cells from these mice bound CTLA-4 and GL1 monoclonal antibody, demonstrating that alternative CTLA-4 ligand or ligands exist. These receptors are functionally important because the residual allogenic mixed lymphocyte responses were blocked by CTLA4Ig. Characterization of these CTLA-4 ligands should lead to strategies for manipulating the immune response.
authors.affiliation: Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Freeman
authors.forename: F
authors.initials: F
authors.lastname: Borriello
authors.forename: R J
authors.initials: RJ
authors.lastname: Hodes
authors.forename: H
authors.initials: H
authors.lastname: Reiser
authors.forename: K S
authors.initials: KS
authors.lastname: Hathcock
authors.forename: G
authors.initials: G
authors.lastname: Laszlo
authors.forename: A J
authors.initials: AJ
authors.lastname: McKnight
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.forename: L
authors.initials: L
authors.lastname: Du
authors.forename: D B
authors.initials: DB
authors.lastname: Lombard
mesh_terms: D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology*; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D060908:CTLA-4 Antigen; D002460:Cell Line; D018796:Immunoconjugates; D007376:Interleukin-2 / Q000378:metabolism; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007376:Interleukin-2; D007519:Isoantigens; D000069594:Abatacept