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

• Published in: International immunology Vol. 11; no. 1; pp. 81 - 88
• Main Authors: Imai, Toshio, Nagira, Morio, Takagi, Shin, Kakizaki, Mayumi, Nishimura, Miyuki, Wang, Jianbin, Gray, Patrick W., Matsushima, Kouji, Yoshie, Osamu
• Format: Journal Article
• Language: English
• Published: England Oxford Publishing Limited (England) 01.01.1999
• Subjects: 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
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/11.1.81

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.