title: Cutting Edge: Ikaros null thymocytes mature into the CD4 lineage with reduced TCR signal: A study using CD3{zeta} immunoreceptor tyrosine-based activation motif transgenic mice.
abstract: Positive selection is a critical T cell developmental checkpoint that is driven by TCR signals. Enhanced positive selection toward the CD4 lineage occurs in the absence of Ikaros. One explanation for this phenotype is that Ikaros establishes the TCR signaling threshold that must be overcome for positive selection to occur. In the current study, this possibility is explored through the use of CD3zeta ITAM transgenic mice that express a CD3 zeta-chain with zero, one, or three ITAMs and an MHC class II (DO11.10)- or MHC class I (H-Y)-restricted TCR transgene. Using this system, we demonstrate that in the absence of Ikaros, thymocytes are able to mature into the CD4 lineage with reduced TCR signaling potential compared with that required to drive the maturation of wild-type thymocytes. We also demonstrate that maturation into the CD8 lineage is enhanced under conditions of reduced TCR signaling potential in the absence of Ikaros.
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Urban
authors.forename: William
authors.initials: W
authors.lastname: Brugmann
authors.forename: Susan
authors.initials: S
authors.lastname: Winandy
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D015153:Blotting, Western; D017252:CD3 Complex / Q000235:genetics* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D051740:Ikaros Transcription Factor / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor