title: T cell development in mice lacking all T cell receptor zeta family members (Zeta, eta, and FcepsilonRIgamma).
abstract: The zeta family includes zeta, eta, and FcepsilonRIgamma (Fcgamma). Dimers of the zeta family proteins function as signal transducing subunits of the T cell antigen receptor (TCR), the pre-TCR, and a subset of Fc receptors. In mice lacking zeta/eta chains, T cell development is impaired, yet low numbers of CD4+ and CD8+ T cells develop. This finding suggests either that pre-TCR and TCR complexes lacking a zeta family dimer can promote T cell maturation, or that in the absence of zeta/eta, Fcgamma serves as a subunit in TCR complexes. To elucidate the role of zeta family dimers in T cell development, we generated mice lacking expression of all of these proteins and compared their phenotype to mice lacking only zeta/eta or Fcgamma. The data reveal that surface complexes that are expressed in the absence of zeta family dimers are capable of transducing signals required for alpha/beta-T cell development. Strikingly, T cells generated in both zeta/eta-/- and zeta/eta-/--Fcgamma-/- mice exhibit a memory phenotype and elaborate interferon gamma. Finally, examination of different T cell populations reveals that zeta/eta and Fcgamma have distinct expression patterns that correlate with their thymus dependency. A possible function for the differential expression of zeta family proteins may be to impart distinctive signaling properties to TCR complexes expressed on specific T cell populations.
authors.affiliation: Division of Hematologic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892. shoresew@helix.nih.gov
authors.forename: E W
authors.initials: EW
authors.lastname: Shores
authors.forename: M
authors.initials: M
authors.lastname: Ono
authors.forename: T
authors.initials: T
authors.lastname: Kawabe
authors.forename: C L
authors.initials: CL
authors.lastname: Sommers
authors.forename: T
authors.initials: T
authors.lastname: Tran
authors.forename: K
authors.initials: K
authors.lastname: Lui
authors.forename: M C
authors.initials: MC
authors.lastname: Udey
authors.forename: J
authors.initials: J
authors.lastname: Ravetch
authors.forename: P E
authors.initials: PE
authors.lastname: Love
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D019281:Dimerization; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D007371:Interferon-gamma / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000172:deficiency*; D015398:Signal Transduction / Q000502:physiology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000276:immunology
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma