title: Maintenance and polarization of human TH2 central memory T cells by thymic stromal lymphopoietin-activated dendritic cells.
abstract: The identity of TH2 memory cells and the mechanism regulating their maintenance during allergic inflammation remain elusive. We report that circulated human CD4+ T cells expressing the prostaglandin D2 receptor (CRTH2) are TH2 central memory T cells, characterized by their phenotype, TH2 cytokine production, gene-expression profile, and the ability to respond to allergens. Only dendritic cells (DCs) activated by thymic stromal lymphopoietin (TSLP) can induce a robust expansion of CRTH2+CD4+ TH2 memory cells, while maintaining their central memory phenotype and TH2 commitments. CRTH2+CD4+ TH2 memory cells activated by TSLP-DCs undergo further TH2 polarization and express cystatin A, Charcot-Leydon crystal protein, and prostaglandin D2 synthase, implying their broader roles in allergic inflammation. Infiltrated CRTH2+CD4+ TH2 effector memory T cells in skin lesion of atopic dermatitis were associated with activated DCs, suggesting that TSLP-DCs play important roles not only in TH2 priming, but also in the maintenance and further polarization of TH2 central memory cells in allergic diseases.
authors.affiliation: Department of Immunology, Center of Cancer Immunology Research, Graduate School of Biomedical Science, Houston, Texas 77030.
authors.forename: Yui-Hsi
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Department of Immunology, Center of Cancer Immunology Research, Graduate School of Biomedical Science, Houston, Texas 77030.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Ito
authors.affiliation: Department of Immunology, Center of Cancer Immunology Research, Graduate School of Biomedical Science, Houston, Texas 77030.
authors.forename: Yi-Hong
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Heinrich-Heine-University, Düsseldorf 40225, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Homey
authors.affiliation: Department of Immunology, Center of Cancer Immunology Research, Graduate School of Biomedical Science, Houston, Texas 77030.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Watanabe
authors.affiliation: Tanox, Inc., Houston, Texas 77025.
authors.forename: Rachel
authors.initials: R
authors.lastname: Martin
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Barnes
authors.affiliation: Department of Immunology, Center of Cancer Immunology Research, Graduate School of Biomedical Science, Houston, Texas 77030.
authors.forename: Bradley W
authors.initials: BW
authors.lastname: McIntyre
authors.affiliation: Department of Immunology, Center of Cancer Immunology Research, Graduate School of Biomedical Science, Houston, Texas 77030.
authors.forename: Michel
authors.initials: M
authors.lastname: Gilliet
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Tanox, Inc., Houston, Texas 77025.
authors.forename: Zhengbin
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Department of Immunology, Center of Cancer Immunology Research, Graduate School of Biomedical Science, Houston, Texas 77030. Electronic address: yjliu@mdanderson.org.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
mesh_terms: D000943:Antigens, Differentiation / Q000378:metabolism; D016764:Cell Polarity / Q000235:genetics; D002478:Cells, Cultured; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000235:genetics / Q000378:metabolism; D015891:Cystatins / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D003876:Dermatitis, Atopic / Q000235:genetics / Q000276:immunology*; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics; D019746:Intramolecular Oxidoreductases / Q000235:genetics; D054834:Lipocalins; D008213:Lymphocyte Activation / Q000235:genetics; D008245:Lysophospholipase / Q000235:genetics; D008562:Membrane Glycoproteins / Q000378:metabolism; D053278:OX40 Ligand; D011971:Receptors, Immunologic / Q000032:analysis / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000032:analysis / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology*; D048069:Tumor Necrosis Factors / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000943:Antigens, Differentiation; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D015891:Cystatins; D016207:Cytokines; D006023:Glycoproteins; D054834:Lipocalins; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; C406562:OX40Ig; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C089251:TNFSF4 protein, human; D048069:Tumor Necrosis Factors; D008245:Lysophospholipase; C011711:lysolecithin acylhydrolase; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; C036293:prostaglandin D2 receptor; D000094632:Thymic Stromal Lymphopoietin