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Science 26 September 1997:
Vol. 277. no. 5334, pp. 2005 - 2007
DOI: 10.1126/science.277.5334.2005
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Reports

Selective Expression of the Eotaxin Receptor CCR3 by Human T Helper 2 Cells

Federica Sallusto, * Charles R. Mackay, dagger Antonio Lanzavecchia

There is growing evidence that T helper cell subsets (TH1 and TH2) can be differentially recruited to promote different types of inflammatory reactions. Murine TH1 but not TH2 cells are recruited through P- and E-selectin into inflamed tissues, where they induce delayed-type hypersensitivity reactions. The human eotaxin-receptor CCR3, originally described on eosinophils and basophils, was also found to be expressed by TH2 cells. An antibody to CCR3 was used to isolate T cells from peripheral blood that give rise to TH2-polarized cell lines and to identify TH2 cells derived from naïve T cells in vitro. Eotaxin stimulated increases in intracellular calcium and chemotaxis of CCR3+ T cells. The attraction of TH2 cells by eotaxin could represent a key mechanism in allergic reactions, because it promotes the allergen-driven production of interleukin-4 and interleukin-5 necessary to activate basophils and eosinophils.

F. Sallusto and A. Lanzavecchia, Basel Institute for Immunology, Grenzacherstrasse 487, CH-4005 Basel, Switzerland.
C. R. MacKay, LeukoSite Inc., Cambridge, MA 02142, USA.
*   To whom correspondence should be addressed. E-mail: sallusto{at}bii.ch

dagger    Present address: Millennium Biotherapeutics Inc., Cambridge, MA 02142, USA.

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The Role of Mitogen-Activated Protein Kinases in Eotaxin-Induced Cytokine Production from Bronchial Epithelial Cells.
C.-H. Cui, T. Adachi, H. Oyamada, Y. Kamada, T. Kuwasaki, Y. Yamada, N. Saito, H. Kayaba, and J. Chihara (2002)
Am. J. Respir. Cell Mol. Biol. 27, 329-335
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Eotaxin (CCL11) and Eotaxin-2 (CCL24) Induce Recruitment of Eosinophils, Basophils, Neutrophils, and Macrophages As Well As Features of Early- and Late-Phase Allergic Reactions Following Cutaneous Injection in Human Atopic and Nonatopic Volunteers.
A. Menzies-Gow, S. Ying, I. Sabroe, V. L. Stubbs, D. Soler, T. J. Williams, and A. B. Kay (2002)
J. Immunol. 169, 2712-2718
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Population analysis of CD4+ T cell chemokine receptor transcript expression during in vivo type-1 (mycobacterial) and type-2 (schistosomal) immune responses.
B.-C. Chiu, X.-Z. Shang, V. R. Stolberg, E. Komuniecki, and S. W. Chensue (2002)
J. Leukoc. Biol. 72, 363-372
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Chemokines and chemokine receptors in leukocyte trafficking.
T. S. Olson and K. Ley (2002)
Am J Physiol Regulatory Integrative Comp Physiol 283, R7-R28
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Eosinophil Recruitment in Type-2 Hypersensitivity Pulmonary Granulomas : Source and Contribution of Monocyte Chemotactic Protein-3 (CCL7).
X.-Z. Shang, B.-C. Chiu, V. Stolberg, N. W. Lukacs, S. L. Kunkel, H. S. Murphy, and S. W. Chensue (2002)
Am. J. Pathol. 161, 257-266
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Eotaxin/CCL11 is involved in acute, but not chronic, allergic airway responses to Aspergillus fumigatus.
J. M. Schuh, K. Blease, S. L. Kunkel, and C. M. Hogaboam (2002)
Am J Physiol Lung Cell Mol Physiol 283, L198-L204
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Responses of Leukocytes to Chemokines in Whole Blood and Their Antagonism by Novel CC-Chemokine Receptor 3 Antagonists.
S. A. Bryan, P. J. Jose, J. R. Topping, R. Wilhelm, C. Soderberg, D. Kertesz, P. J. Barnes, T. J. Williams, T. T. Hansel, and I. Sabroe (2002)
Am. J. Respir. Crit. Care Med. 165, 1602-1609
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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.
K. Sato, H. Kawasaki, C. Morimoto, N. Yamashima, and T. Matsuyama (2002)
J. Immunol. 168, 6263-6272
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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.
O. Fahy, S. Senechal, J. Pene, A. Scherpereel, P. Lassalle, A.-B. Tonnel, H. Yssel, B. Wallaert, and A. Tsicopoulos (2002)
J. Immunol. 168, 5912-5919
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Patterns of Chemokine Receptor Expression on Peripheral Blood {gamma}{delta} T Lymphocytes: Strong Expression of CCR5 Is a Selective Feature of V{delta}2/V{gamma}9 {gamma}{delta} T Cells.
A. Glatzel, D. Wesch, F. Schiemann, E. Brandt, O. Janssen, and D. Kabelitz (2002)
J. Immunol. 168, 4920-4929
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IL-16 Promotes Leukotriene C4 and IL-4 Release from Human Eosinophils via CD4- and Autocrine CCR3-Chemokine-Mediated Signaling.
C. Bandeira-Melo, K. Sugiyama, L. J. Woods, M. Phoofolo, D. M. Center, W. W. Cruikshank, and P. F. Weller (2002)
J. Immunol. 168, 4756-4763
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Increased expression of the inflammatory chemokine CXC chemokine ligand 9/monokine induced by interferon-gamma in lymphoid tissues of rhesus macaques during simian immunodeficiency virus infection and acquired immunodeficiency syndrome.
T. A. Reinhart, B. A. Fallert, M. E. Pfeifer, S. Sanghavi, S. Capuano III, P. Rajakumar, M. Murphey-Corb, R. Day, C. L. Fuller, and T. M Schaefer (2002)
Blood 99, 3119-3128
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Germinal Center B Cells Constitute a Predominant Physiological Source of IL-4: Implication for Th2 Development In Vivo.
B. Johansson-Lindbom and C. A. K. Borrebaeck (2002)
J. Immunol. 168, 3165-3172
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Eotaxin/CCL11 Suppresses IL-8/CXCL8 Secretion from Human Dermal Microvascular Endothelial Cells.
S. S. Cheng, N. W. Lukacs, and S. L. Kunkel (2002)
J. Immunol. 168, 2887-2894
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Eotaxin-2 Generation Is Differentially Regulated by Lipopolysaccharide and IL-4 in Monocytes and Macrophages.
K. Watanabe, P. J. Jose, and S. M. Rankin (2002)
J. Immunol. 168, 1911-1918
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The murine CCR3 receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyperresponsiveness.
A. A. Humbles, B. Lu, D. S. Friend, S. Okinaga, J. Lora, A. Al-garawi, T. R. Martin, N. P. Gerard, and C. Gerard (2002)
PNAS 99, 1479-1484
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Chemokine and Chemokine Receptor Dynamics during Genital Chlamydial Infection.
T. Belay, F. O. Eko, G. A. Ananaba, S. Bowers, T. Moore, D. Lyn, and J. U. Igietseme (2002)
Infect. Immun. 70, 844-850
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Accumulation of CRTH2-positive T-helper 2 and T-cytotoxic 2 cells at implantation sites of human decidua in a prostaglandin D2-mediated manner.
T. Michimata, H. Tsuda, M. Sakai, M. Fujimura, K. Nagata, M. Nakamura, and S. Saito (2002)
Mol. Hum. Reprod. 8, 181-187
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CCL7 and CXCL10 Orchestrate Oxidative Stress-Induced Neutrophilic Lung Inflammation.
L. Michalec, B. K. Choudhury, E. Postlethwait, J. S. Wild, R. Alam, M. Lett-Brown, and S. Sur (2002)
J. Immunol. 168, 846-852
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Dendritic Cells: Immune Regulators in Health and Disease.
M. F. Lipscomb and B. J. Masten (2002)
Physiol Rev 82, 97-130
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IP-10 and Mig Production by Glomerular Cells in Human Proliferative Glomerulonephritis and Regulation by Nitric Oxide.
P. Romagnani, E. Lazzeri, L. Lasagni, C. Mavilia, C. Beltrame, M. Francalanci, M. Rotondi, F. Annunziato, L. Maurenzig, L. Cosmi, et al. (2002)
J. Am. Soc. Nephrol. 13, 53-64
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The CC Chemokine Eotaxin (CCL11) Is a Partial Agonist of CC Chemokine Receptor 2b.
R. Martinelli, I. Sabroe, G. LaRosa, T. J. Williams, and J. E. Pease (2001)
J. Biol. Chem. 276, 42957-42964
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Functional and Antigenic Characterization of Human, Rhesus Macaque, Pigtailed Macaque, and Murine DC-SIGN.
F. Baribaud, S. Pohlmann, T. Sparwasser, M. T. Y. Kimata, Y.-K. Choi, B. S. Haggarty, N. Ahmad, T. Macfarlan, T. G. Edwards, G. J. Leslie, et al. (2001)
J. Virol. 75, 10281-10289
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IL-4 differentially regulates eotaxin and MCP-4 in lung epithelium and circulating mononuclear cells.
H. Nakamura, A. D. Luster, H. Tateno, S. Jedrzkiewicz, G. Tamura, K. J. Haley, E. A. Garcia-Zepeda, K. Yamaguchi, and C. M. Lilly (2001)
Am J Physiol Lung Cell Mol Physiol 281, L1288-L1302
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Expression of chemokine receptors in vernal keratoconjunctivitis.
A. M A. El-Asrar, S. Struyf, A. A Al-Mosallam, L. Missotten, J. Van Damme, and K. Geboes (2001)
Br J Ophthalmol 85, 1357-1361
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