title: Induction of T helper type 2 immunity by a point mutation in the LAT adaptor.
abstract: The transmembrane protein LAT (linker for activation of T cells) couples the T cell receptor (TCR) to downstream signaling effectors. Mice homozygous for a mutation of a single LAT tyrosine residue showed impeded T cell development. However, later they accumulated polyclonal helper T (TH) cells that chronically produced type 2 cytokines in large amounts. This exaggerated TH2 differentiation caused tissue eosinophilia and massive maturation of plasma cells secreting to immunoglobulins of the E and G1 isotypes. This paradoxical phenotype establishes an unanticipated inhibitory function for LAT that is critical for the differentiation and homeostasis of TH cells.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, INSERM- and CNRS-Université de la Méditerranée, Parc Scientifique de Luminy, 13288 Marseille Cedex 9, France.
authors.forename: Enrique
authors.initials: E
authors.lastname: Aguado
authors.forename: Sylvie
authors.initials: S
authors.lastname: Richelme
authors.forename: Selene
authors.initials: S
authors.lastname: Nuñez-Cruz
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Miazek
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Mura
authors.forename: Mireille
authors.initials: M
authors.lastname: Richelme
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Guo
authors.forename: Danielle
authors.initials: D
authors.lastname: Sainty
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: He
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.forename: Marie
authors.initials: M
authors.lastname: Malissen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D018956:CD5 Antigens / Q000032:analysis / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology*; D002453:Cell Cycle; D002454:Cell Differentiation; D004802:Eosinophilia; D004804:Eosinophils / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics* / Q000502:physiology*; D017354:Point Mutation; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000502:physiology; D018418:Th2 Cells / Q000276:immunology* / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018956:CD5 Antigens; D002352:Carrier Proteins; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007378:Interleukins; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D007073:Immunoglobulin E; D007371:Interferon-gamma