Maintenance and polarization of human TH2 central memory T cells by thymic stromal lymphopoietin-activated dendritic cells

Yui-Hsi Wang; Tomoki Ito; Yi-Hong Wang; Bernhard Homey; Norihiko Watanabe; Rachel Martin; Christopher J Barnes; Bradley W McIntyre; Michel Gilliet; Rakesh Kumar; Zhengbin Yao; Yong-Jun Liu

doi:10.1016/j.immuni.2006.03.019

Maintenance and polarization of human TH2 central memory T cells by thymic stromal lymphopoietin-activated dendritic cells

Immunity. 2006 Jun;24(6):827-838. doi: 10.1016/j.immuni.2006.03.019.

Authors

Affiliations

¹ Department of Immunology, Center of Cancer Immunology Research, Graduate School of Biomedical Science, Houston, Texas 77030.
² Department of Dermatology, Heinrich-Heine-University, Düsseldorf 40225, Germany.
³ Tanox, Inc., Houston, Texas 77025.
⁴ Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030.
⁵ Department of Immunology, Center of Cancer Immunology Research, Graduate School of Biomedical Science, Houston, Texas 77030. Electronic address: [email protected].

PMID: 16782037
DOI: 10.1016/j.immuni.2006.03.019

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigens, Differentiation / metabolism
Cell Polarity / genetics
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor Proteins / genetics
Cyclin-Dependent Kinase Inhibitor Proteins / metabolism
Cystatins / genetics
Cytokines / genetics
Cytokines / pharmacology*
Dendritic Cells / drug effects*
Dendritic Cells / immunology
Dermatitis, Atopic / genetics
Dermatitis, Atopic / immunology*
Gene Expression Profiling
Glycoproteins / genetics
Humans
Immunologic Memory* / genetics
Intramolecular Oxidoreductases / genetics
Lipocalins
Lymphocyte Activation / genetics
Lysophospholipase / genetics
Membrane Glycoproteins / metabolism
OX40 Ligand
Receptors, Immunologic / analysis
Receptors, Immunologic / metabolism*
Receptors, Prostaglandin / analysis
Receptors, Prostaglandin / metabolism*
Th2 Cells / immunology*
Thymic Stromal Lymphopoietin
Tumor Necrosis Factors / metabolism

Substances

Antigens, Differentiation
Cyclin-Dependent Kinase Inhibitor Proteins
Cystatins
Cytokines
Glycoproteins
Lipocalins
Membrane Glycoproteins
OX40 Ligand
OX40Ig
Receptors, Immunologic
Receptors, Prostaglandin
TNFSF4 protein, human
Tumor Necrosis Factors
Lysophospholipase
lysolecithin acylhydrolase
Intramolecular Oxidoreductases
prostaglandin R2 D-isomerase
prostaglandin D2 receptor
Thymic Stromal Lymphopoietin