title: T cell factor-1 and β-catenin control the development of memory-like CD8 thymocytes.
abstract: Innate memory-like CD8 thymocytes develop and acquire effector function during maturation in the absence of encounter with Ags. In this study, we demonstrate that enhanced function of transcription factors T cell factor (TCF)-1 and β-catenin regulate the frequency of promyelocytic leukemia zinc finger (PLZF)-expressing, IL-4-producing thymocytes that promote the generation of eomesodermin-expressing memory-like CD8 thymocytes in trans. In contrast, TCF1-deficient mice do not have PLZF-expressing thymocytes and eomesodermin-expressing memory-like CD8 thymocytes. Generation of TCF1 and β-catenin-dependent memory-like CD8 thymocytes is non-cell-intrinsic and requires the expression of IL-4 and IL-4R. CD8 memory-like thymocytes migrate to the peripheral lymphoid organs, and the memory-like CD8 T cells rapidly produce IFN-γ. Thus, TCF1 and β-catenin regulate the generation of PLZF-expressing thymocytes and thereby facilitate the generation of memory-like CD8 T cells in the thymus.
authors.affiliation: Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Archna
authors.initials: A
authors.lastname: Sharma
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Chen
authors.forename: Trang
authors.initials: T
authors.lastname: Nguyen
authors.forename: Qing
authors.initials: Q
authors.lastname: Yu
authors.forename: Jyoti Misra
authors.initials: JM
authors.lastname: Sen
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D051538:Hepatocyte Nuclear Factor 1-alpha; D006801:Humans; D007113:Immunity, Innate; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D051822:T Cell Transcription Factor 1 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology; D060168:Thymocytes / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D051176:beta Catenin / Q000235:genetics / Q000276:immunology*
chemical_list: D016827:CD8 Antigens; C491198:Eomes protein, mouse; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; D051741:Kruppel-Like Transcription Factors; D019948:Receptors, Interleukin-4; D051822:T Cell Transcription Factor 1; D020825:T-Box Domain Proteins; D051176:beta Catenin; D015847:Interleukin-4; D007371:Interferon-gamma