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

Immunity. 2006 Jun;24(6):827-38. 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*
  • 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
  • thymic stromal lymphopoietin
  • prostaglandin D2 receptor