Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine.
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.
Shionogi Institute for Medical Science, Settsu, Osaka, Japan.
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T
Imai
M
M
Nagira
S
S
Takagi
M
M
Kakizaki
M
M
Nishimura
J
J
Wang
P W
PW
Gray
K
K
Matsushima
O
O
Yoshie
D000938:Antigen-Presenting Cells / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte; D015496:CD4-Positive T-Lymphocytes; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D018925:Chemokines / Q000276:immunology*; D019742:Chemokines, CC / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D003713:Dendritic Cells / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007156:Immunologic Memory; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D017493:Leukocyte Common Antigens; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000276:immunology*; D016176:T-Lymphocyte Subsets; D018418:Th2 Cells / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; C106230:CCL17 protein, human; C515482:CCL22 protein, human; C515354:CCR4 protein, human; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D018925:Chemokines; D019742:Chemokines, CC; D007377:Interleukin-3; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017493:Leukocyte Common Antigens