Maintenance and polarization of human TH2 central memory T cells by thymic stromal lymphopoietin-activated dendritic cells.
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.
Wang
Yui-Hsi
YH
Department of Immunology, Center of Cancer Immunology Research, Graduate School of Biomedical Science, Houston, Texas 77030.
Ito
Tomoki
T
Department of Immunology, Center of Cancer Immunology Research, Graduate School of Biomedical Science, Houston, Texas 77030.
Wang
Yi-Hong
YH
Department of Immunology, Center of Cancer Immunology Research, Graduate School of Biomedical Science, Houston, Texas 77030.
Homey
Bernhard
B
Department of Dermatology, Heinrich-Heine-University, Düsseldorf 40225, Germany.
Watanabe
Norihiko
N
Department of Immunology, Center of Cancer Immunology Research, Graduate School of Biomedical Science, Houston, Texas 77030.
Martin
Rachel
R
Tanox, Inc., Houston, Texas 77025.
Barnes
Christopher J
CJ
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030.
McIntyre
Bradley W
BW
Department of Immunology, Center of Cancer Immunology Research, Graduate School of Biomedical Science, Houston, Texas 77030.
Gilliet
Michel
M
Department of Immunology, Center of Cancer Immunology Research, Graduate School of Biomedical Science, Houston, Texas 77030.
Kumar
Rakesh
R
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030.
Yao
Zhengbin
Z
Tanox, Inc., Houston, Texas 77025.
Liu
Yong-Jun
YJ
Department of Immunology, Center of Cancer Immunology Research, Graduate School of Biomedical Science, Houston, Texas 77030. Electronic address: yjliu@mdanderson.org.
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
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