title: Costimulation through the inducible costimulator ligand is essential for both T helper and B cell functions in T cell-dependent B cell responses.
abstract: Costimulation through the inducible costimulator (ICOS) and its ligand (ICOSL) is essential for T cell-dependent B cell responses, but the cellular and temporal dynamics underlying its in vivo effects are poorly defined. Here we have shown that Icosl(-/-) and Icos(-/-) mice had similar phenotypes and that ICOS-ICOSL costimulation modulated the early but not late phases of IgG1 affinity maturation. Exploiting the adoptive transfer of T or B cells from primed Icosl(-/-) mice, we provided genetic evidence that costimulation through ICOSL was essential for primary but not secondary helper T cell responses and for the control of both T and B cell activities, resulting in T cell-dependent IgG1 production.
authors.affiliation: Advanced Medical Discovery Institute, and Ontario Cancer Institute, Department of Medical Biophysics , University of Toronto, Toronto, Ontario M5G 2C1, Canada. tmak@uhnres.utoronto.ca
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
authors.forename: Arda
authors.initials: A
authors.lastname: Shahinian
authors.forename: Steve K
authors.initials: SK
authors.lastname: Yoshinaga
authors.forename: Andrew
authors.initials: A
authors.lastname: Wakeham
authors.forename: Louis-Martin
authors.initials: LM
authors.lastname: Boucher
authors.forename: Melania
authors.initials: M
authors.lastname: Pintilie
authors.forename: Gordon
authors.initials: G
authors.lastname: Duncan
authors.forename: Beata U
authors.initials: BU
authors.lastname: Gajewska
authors.forename: Matthew
authors.initials: M
authors.lastname: Gronski
authors.forename: Urs
authors.initials: U
authors.lastname: Eriksson
authors.forename: Bernhard
authors.initials: B
authors.lastname: Odermatt
authors.forename: Alexandra
authors.initials: A
authors.lastname: Ho
authors.forename: Denis
authors.initials: D
authors.lastname: Bouchard
authors.forename: John S
authors.initials: JS
authors.lastname: Whorisky
authors.forename: Manel
authors.initials: M
authors.lastname: Jordana
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Ohashi
authors.forename: Tony
authors.initials: T
authors.lastname: Pawson
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Bladt
authors.forename: Anna
authors.initials: A
authors.lastname: Tafuri
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D017353:Gene Deletion; D007074:Immunoglobulin G / Q000276:immunology; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D008211:Lymphocyte Cooperation / Q000276:immunology*; D051379:Mice; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; C556694:Icos protein, mouse; C400230:Icosl protein, mouse; D007074:Immunoglobulin G; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D011506:Proteins