title: The CD4-related molecule, LAG-3 (CD223), regulates the expansion of activated T cells.
abstract: The lymphocyte activation gene-3 (LAG-3, CD223) is a CD4-related, activation-induced cell surface molecule that binds to MHC class II with high affinity. The function of murine LAG-3 on T cells is unclear. Here, we show that V beta 7/8(+)LAG-3(-/-) T cells expand poorly following staphylococcal enterotoxin B (SEB) stimulation in vitro. LAG-3(-/-) T cells proliferate at a normal rate, but exhibit increased cell death. Similar observations were made with LAG-3(-/-)CD4(+)OT-II TCR transgenic T cells following peptide stimulation. Despite reduced T cell expansion and increased cell death, LAG-3(-/-)OT-II(+) T cells secrete more IL-2 and IFN-gamma following stimulation. Antigen-driven expansion of LAG-3(-/-) T cells was restored by constitutive expression of LAG-3 via retroviral-mediated stem cell gene transfer. We further show that LAG-3 function is mediated via its cytoplasmic domain, for which a conserved 'KIEELE' motif is essential. Our data support a role for LAG-3 in regulating the expansion of activated T cells.
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.
authors.forename: Creg J
authors.initials: CJ
authors.lastname: Workman
authors.forename: Dario A A
authors.initials: DA
authors.lastname: Vignali
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D015704:CD4 Antigens / Q000737:chemistry; D016923:Cell Death; D004768:Enterotoxins / Q000494:pharmacology; D019672:Genes, T-Cell Receptor; D006801:Humans; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; D015704:CD4 Antigens; D004768:Enterotoxins; D008565:Membrane Proteins; C031818:enterotoxin B, staphylococcal; D000093322:Lymphocyte Activation Gene 3 Protein