International Immunology, Vol. 11, No. 1, 81-88,
January 1999
© 1999 Japanese Society for Immunology
Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine
Shionogi Institute for Medical Science, 2-5-1 Mishima, Settsu, Osaka 566-0022, Japan
1 Department of Molecular Preventive Medicine, School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
2 ICOS Corp., 22021 20th Avenue SE, Bothell WA 98021, USA
Correspondence to: T. Imai
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 ~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.
Keywords: chemokine, chemokine receptor, chemotaxis, dendritic cells, Th2 cells, transendothelial migration
Transmitting editor: M. Miyasaka
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C. H. Kim, B. Johnston, and E. C. Butcher Trafficking machinery of NKT cells: shared and differential chemokine receptor expression among Valpha 24+Vbeta 11+ NKT cell subsets with distinct cytokine-producing capacity Blood, June 17, 2002; 100(1): 11 - 16. [Abstract] [Full Text] [PDF]
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M. Nishimura, H. Umehara, T. Nakayama, O. Yoneda, K. Hieshima, M. Kakizaki, N. Dohmae, O. Yoshie, and T. Imai Dual Functions of Fractalkine/CX3C Ligand 1 in Trafficking of Perforin+/Granzyme B+ Cytotoxic Effector Lymphocytes That Are Defined by CX3CR1 Expression J. Immunol., June 15, 2002; 168(12): 6173 - 6180. [Abstract] [Full Text] [PDF]
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K. Sato, H. Kawasaki, C. Morimoto, N. Yamashima, and T. Matsuyama An Abortive Ligand-Induced Activation of CCR1-Mediated Downstream Signaling Event and a Deficiency of CCR5 Expression Are Associated with the Hyporesponsiveness of Human Naive CD4+ T Cells to CCL3 and CCL5 J. Immunol., June 15, 2002; 168(12): 6263 - 6272. [Abstract] [Full Text] [PDF]
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O. Fahy, S. Senechal, J. Pene, A. Scherpereel, P. Lassalle, A.-B. Tonnel, H. Yssel, B. Wallaert, and A. Tsicopoulos Diesel Exposure Favors Th2 Cell Recruitment by Mononuclear Cells and Alveolar Macrophages from Allergic Patients by Differentially Regulating Macrophage-Derived Chemokine and IFN-{gamma}-Induced Protein-10 Production J. Immunol., June 1, 2002; 168(11): 5912 - 5919. [Abstract] [Full Text] [PDF]
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B. F. Skinnider and T. W. Mak The role of cytokines in classical Hodgkin lymphoma Blood, May 29, 2002; 99(12): 4283 - 4297. [Abstract] [Full Text] [PDF]
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E. Miyazaki, S.-i. Nureki, T. Fukami, T. Shigenaga, M. Ando, K. Ito, H. Ando, K. Sugisaki, T. Kumamoto, and T. Tsuda Elevated Levels of Thymus- and Activation-regulated Chemokine in Bronchoalveolar Lavage Fluid from Patients with Eosinophilic Pneumonia Am. J. Respir. Crit. Care Med., April 15, 2002; 165(8): 1125 - 1131. [Abstract] [Full Text] [PDF]
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Z. Zhu, B. Ma, T. Zheng, R. J. Homer, C. G. Lee, I. F. Charo, P. Noble, and J. A. Elias IL-13-Induced Chemokine Responses in the Lung: Role of CCR2 in the Pathogenesis of IL-13-Induced Inflammation and Remodeling J. Immunol., March 15, 2002; 168(6): 2953 - 2962. [Abstract] [Full Text] [PDF]
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O. Yoshie, R. Fujisawa, T. Nakayama, H. Harasawa, H. Tago, D. Izawa, K. Hieshima, Y. Tatsumi, K. Matsushima, H. Hasegawa, et al. Frequent expression of CCR4 in adult T-cell leukemia and human T-cell leukemia virus type 1-transformed T cells Blood, March 1, 2002; 99(5): 1505 - 1511. [Abstract] [Full Text] [PDF]
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 T. Michimata, H. Tsuda, M. Sakai, M. Fujimura, K. Nagata, M. Nakamura, and S. Saito Accumulation of CRTH2-positive T-helper 2 and T-cytotoxic 2 cells at implantation sites of human decidua in a prostaglandin D2-mediated manner Mol. Hum. Reprod., February 1, 2002; 8(2): 181 - 187. [Abstract] [Full Text] [PDF]
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E. J. Kunkel, J. Boisvert, K. Murphy, M. A. Vierra, M. C. Genovese, A. J. Wardlaw, H. B. Greenberg, M. R. Hodge, L. Wu, E. C. Butcher, et al. Expression of the Chemokine Receptors CCR4, CCR5, and CXCR3 by Human Tissue-Infiltrating Lymphocytes Am. J. Pathol., January 1, 2002; 160(1): 347 - 355. [Abstract] [Full Text] [PDF]
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A. Biragyn, M. Surenhu, D. Yang, P. A. Ruffini, B. A. Haines, E. Klyushnenkova, J. J. Oppenheim, and L. W. Kwak Mediators of Innate Immunity That Target Immature, But Not Mature, Dendritic Cells Induce Antitumor Immunity When Genetically Fused with Nonimmunogenic Tumor Antigens J. Immunol., December 1, 2001; 167(11): 6644 - 6653. [Abstract] [Full Text] [PDF]
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K. Hase, K. Tani, T. Shimizu, Y. Ohmoto, K. Matsushima, and S. Sone Increased CCR4 expression in active systemic lupus erythematosus J. Leukoc. Biol., November 1, 2001; 70(5): 749 - 755. [Abstract] [Full Text] [PDF]
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 S. W. Chensue Molecular Machinations: Chemokine Signals in Host-Pathogen Interactions Clin. Microbiol. Rev., October 1, 2001; 14(4): 821 - 835. [Abstract] [Full Text] [PDF]
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K. KURASHIMA, M. FUJIMURA, S. MYOU, K. KASAHARA, H. TACHIBANA, N. AMEMIYA, Y. ISHIURA, N. ONAI, K. MATSUSHIMA, and S. NAKAO Effects of Oral Steroids on Blood CXCR3+ and CCR4+ T Cells in Patients with Bronchial Asthma Am. J. Respir. Crit. Care Med., September 1, 2001; 164(5): 754 - 758. [Abstract] [Full Text] [PDF]
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P. Ghia, P. Transidico, J. P. Veiga, C. Schaniel, F. Sallusto, K. Matsushima, S. E. Sallan, A. G. Rolink, A. Mantovani, L. M. Nadler, et al. Chemoattractants MDC and TARC are secreted by malignant B-cell precursors following CD40 ligation and support the migration of leukemia-specific T cells Blood, August 1, 2001; 98(3): 533 - 540. [Abstract] [Full Text] [PDF]
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M. Iikura, M. Miyamasu, M. Yamaguchi, H. Kawasaki, K. Matsushima, M. Kitaura, Y. Morita, O. Yoshie, K. Yamamoto, and K. Hirai Chemokine receptors in human basophils: inducible expression of functional CXCR4 J. Leukoc. Biol., July 1, 2001; 70(1): 113 - 120. [Abstract] [Full Text] [PDF]
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S. D. Thompson, L. K. Luyrink, T. B. Graham, M. Tsoras, M. Ryan, M. H. Passo, and D. N. Glass Chemokine Receptor CCR4 on CD4+ T Cells in Juvenile Rheumatoid Arthritis Synovial Fluid Defines a Subset of Cells with Increased IL-4:IFN-{{gamma}} mRNA Ratios J. Immunol., June 1, 2001; 166(11): 6899 - 6906. [Abstract] [Full Text] [PDF]
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 M. Cecilia Berin, L. Eckmann, D. H. Broide, and M. F. Kagnoff Regulated Production of the T Helper 2-Type T-Cell Chemoattractant TARC by Human Bronchial Epithelial Cells In Vitro and in Human Lung Xenografts Am. J. Respir. Cell Mol. Biol., April 1, 2001; 24(4): 382 - 389. [Abstract] [Full Text]
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F. Katou, H. Ohtani, T. Nakayama, K. Ono, K. Matsushima, A. Saaristo, H. Nagura, O. Yoshie, and K. Motegi Macrophage-Derived Chemokine (MDC/CCL22) and CCR4 Are Involved in the Formation of T Lymphocyte-Dendritic Cell Clusters in Human Inflamed Skin and Secondary Lymphoid Tissue Am. J. Pathol., April 1, 2001; 158(4): 1263 - 1270. [Abstract] [Full Text] [PDF]
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S. Nagai, S.-i. Hashimoto, T. Yamashita, N. Toyoda, T. Satoh, T. Suzuki, and K. Matsushima Comprehensive gene expression profile of human activated Th1- and Th2-polarized cells Int. Immunol., March 1, 2001; 13(3): 367 - 376. [Abstract] [Full Text] [PDF]
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M. Goebeler, A. Trautmann, A. Voss, E.-B. Brocker, A. Toksoy, and R. Gillitzer Differential and Sequential Expression of Multiple Chemokines during Elicitation of Allergic Contact Hypersensitivity Am. J. Pathol., February 1, 2001; 158(2): 431 - 440. [Abstract] [Full Text] [PDF]
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E. Kuroda, T. Sugiura, K. Okada, K. Zeki, and U. Yamashita Prostaglandin E2 Up-Regulates Macrophage-Derived Chemokine Production but Suppresses IFN-Inducible Protein-10 Production by APC J. Immunol., February 1, 2001; 166(3): 1650 - 1658. [Abstract] [Full Text] [PDF]
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K. Sato, H. Kawasaki, H. Nagayama, M. Enomoto, C. Morimoto, K. Tadokoro, T. Juji, and T. A. Takahashi Chemokine Receptor Expressions and Responsiveness of Cord Blood T Cells J. Immunol., February 1, 2001; 166(3): 1659 - 1666. [Abstract] [Full Text] [PDF]
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S. Kawasaki, H. Takizawa, H. Yoneyama, T. Nakayama, R. Fujisawa, M. Izumizaki, T. Imai, O. Yoshie, I. Homma, K. Yamamoto, et al. Intervention of Thymus and Activation-Regulated Chemokine Attenuates the Development of Allergic Airway Inflammation and Hyperresponsiveness in Mice J. Immunol., February 1, 2001; 166(3): 2055 - 2062. [Abstract] [Full Text] [PDF]
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H. Hirai, K. Tanaka, O. Yoshie, K. Ogawa, K. Kenmotsu, Y. Takamori, M. Ichimasa, K. Sugamura, M. Nakamura, S. Takano, et al. Prostaglandin D2 Selectively Induces Chemotaxis in T Helper Type 2 Cells, Eosinophils, and Basophils via Seven-Transmembrane Receptor Crth2 J. Exp. Med., January 15, 2001; 193(2): 255 - 262. [Abstract] [Full Text] [PDF]
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D. P. Andrew, N. Ruffing, C. H. Kim, W. Miao, H. Heath, Y. Li, K. Murphy, J. J. Campbell, E. C. Butcher, and L. Wu C-C Chemokine Receptor 4 Expression Defines a Major Subset of Circulating Nonintestinal Memory T Cells of Both Th1 and Th2 Potential J. Immunol., January 1, 2001; 166(1): 103 - 111. [Abstract] [Full Text] [PDF]
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T. Nanki and P. E. Lipsky Lack of correlation between chemokine receptor and Th1/Th2 cytokine expression by individual memory T cells Int. Immunol., December 1, 2000; 12(12): 1659 - 1667. [Abstract] [Full Text] [PDF]
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J. Yamamoto, Y. Adachi, Y. Onoue, Y. S. Adachi, Y. Okabe, T. Itazawa, M. Toyoda, T. Seki, M. Morohashi, K. Matsushima, et al. Differential expression of the chemokine receptors by the Th1- and Th2-type effector populations within circulating CD4+ T cells J. Leukoc. Biol., October 1, 2000; 68(4): 568 - 574. [Abstract] [Full Text]
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A. Mantovani, P. A. Gray, J. Van Damme, and S. Sozzani Macrophage-derived chemokine (MDC) J. Leukoc. Biol., September 1, 2000; 68(3): 400 - 404. [Abstract] [Full Text] [PDF]
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T. Sekiya, M. Miyamasu, M. Imanishi, H. Yamada, T. Nakajima, M. Yamaguchi, T. Fujisawa, R. Pawankar, Y. Sano, K. Ohta, et al. Inducible Expression of a Th2-Type CC Chemokine Thymus- and Activation-Regulated Chemokine by Human Bronchial Epithelial Cells J. Immunol., August 15, 2000; 165(4): 2205 - 2213. [Abstract] [Full Text] [PDF]
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R. A. Tripp, L. Jones, and L. J. Anderson Respiratory Syncytial Virus G and/or SH Glycoproteins Modify CC and CXC Chemokine mRNA Expression in the BALB/c Mouse J. Virol., July 1, 2000; 74(13): 6227 - 6229. [Abstract] [Full Text]
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A. Matsukawa, C. M. Hogaboam, N. W. Lukacs, P. M. Lincoln, H. L. Evanoff, and S. L. Kunkel Pivotal Role of the CC Chemokine, Macrophage-Derived Chemokine, in the Innate Immune Response J. Immunol., May 15, 2000; 164(10): 5362 - 5368. [Abstract] [Full Text] [PDF]
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J. T. Stine, C. Wood, M. Hill, A. Epp, C. J. Raport, V. L. Schweickart, Y. Endo, T. Sasaki, G. Simmons, C. Boshoff, et al. KSHV-encoded CC chemokine vMIP-III is a CCR4 agonist, stimulates angiogenesis, and selectively chemoattracts TH2 cells Blood, February 15, 2000; 95(4): 1151 - 1157. [Abstract] [Full Text] [PDF]
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L. M. Staudt The Molecular and Cellular Origins of Hodgkin's Disease J. Exp. Med., January 17, 2000; 191(2): 207 - 212. [Full Text] [PDF]
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