Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine

Int Immunol. 1999 Jan;11(1):81-8. doi: 10.1093/intimm/11.1.81.

Abstract

Helper T cells are classified into Th1 and Th2 subsets based on their profiles of cytokine production. Th1 cells are involved in cell-mediated immunity, whereas Th2 cells induce humoral responses. Selective recruitment of these two subsets depends on specific adhesion molecules and specific chemoattractants. Here, we demonstrate that the T cell-directed CC chemokine thymus and activation-regulated chemokine (TARC) was abundantly produced by monocytes treated with granulocyte macrophage colony stimulating factor (GM-CSF) or IL-3, especially in the presence of IL-4 and by dendritic cells derived from monocytes cultured with GM-CSF + IL-4. The receptor for TARC and another macrophage/dendritic cell-derived CC chemokine macrophage-derived chemokine (MDC) is CCR4, a G protein-coupled receptor. CCR4 was found to be expressed on approximately 20% of adult peripheral blood effector/memory CD4+ T cells. T cells attracted by TARC and MDC generated cell lines predominantly producing Th2-type cytokines, IL-4 and IL-5. Fractionated CCR4+ cells but not CCR4- cells also selectively gave rise to Th2-type cell lines. When naive CD4+ T cells from adult peripheral blood were polarized in vitro, Th2-type cells selectively expressed CCR4 and vigorously migrated toward TARC and MDC. Taken together, CCR4 is selectively expressed on Th2-type T cells and antigen-presenting cells may recruit Th2 cells expressing CCR4 by producing TARC and MDC in Th2-dominant conditions.

MeSH terms

  • Antigen-Presenting Cells / immunology*
  • Antigens, Differentiation, T-Lymphocyte
  • CD4-Positive T-Lymphocytes
  • Chemokine CCL17
  • Chemokine CCL22
  • Chemokines / immunology*
  • Chemokines, CC / immunology
  • Chemotaxis, Leukocyte*
  • Dendritic Cells / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Humans
  • Immunologic Memory
  • Interleukin-3 / pharmacology
  • Interleukin-4 / pharmacology
  • Leukocyte Common Antigens
  • Macrophages / immunology
  • Monocytes / immunology
  • Receptors, CCR4
  • Receptors, Chemokine / immunology*
  • T-Lymphocyte Subsets
  • Th2 Cells / immunology*
  • Thymus Gland / immunology*

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • CCL17 protein, human
  • CCL22 protein, human
  • CCR4 protein, human
  • Chemokine CCL17
  • Chemokine CCL22
  • Chemokines
  • Chemokines, CC
  • Interleukin-3
  • Receptors, CCR4
  • Receptors, Chemokine
  • Interleukin-4
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Leukocyte Common Antigens