J. Exp. Med., Volume 187, Number 1, January 5, 1998 129-134

BRIEF DEFINITIVE REPORT:
Differential Expression of Chemokine Receptors and Chemotactic Responsiveness of Type 1 T Helper Cells (Th1s) and Th2s

By Raffaella Bonecchi,^* Giancarlo Bianchi,^* Paola Panina Bordignon, Daniele D'Ambrosio, Rosmarie Lang, Alessandro Borsatti,^* Silvano Sozzani,^* Paola Allavena,^* Patrick A. Gray,^§ Alberto Mantovani,^* and Francesco Sinigaglia

From the ^* Istituto di Ricerche Farmacologiche "Mario Negri", I-20157 Milan, Italy;  Roche Milano Ricerche, I-20132 Milan, Italy; ^§ ICOS Corporation, Bothell, Washington 98021; and  Universita' di Brescia, I-25123 Brescia, Italy

T helper cells type 1 (Th1s) that produce interferon- predominantly mediate cellular immune responses and are involved in the development of chronic inflammatory conditions, whereas Th2s which produce large amounts of IL-4 and IL-5 upregulate IgE production and are prominent in the pathogenesis of allergic diseases. The precise factors determining whether Th1- or Th2-mediated immune responses preferentially occur at a peripheral site of antigen exposure are largely unknown. Chemokines, a superfamily of polypeptide mediators, are a key component of the leukocyte recruitment process. Here we report that among four CXC (CXCR1-4) and five CC (CCR1-5) chemokine receptors analyzed, CXCR3 and CCR5 are preferentially expressed in human Th1s. In contrast, Th2s preferentially express CCR4 and, to a lesser extent, CCR3. In agreement with the differential chemokine receptor expression, Th1s and Th2s selectively migrate in response to the corresponding chemokines. The differential expression of chemokine receptors may dictate, to a large extent, the migration and tissue homing of Th1s and Th2s. It may also determine different susceptibility of Th1s and Th2s to human immunodeficiency virus strains using different fusion coreceptors.

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• Sundrud, M. S., VanCompernolle, S. E., Eger, K. A., Bruno, T. C., Subramaniam, A., Mummidi, S., Ahuja, S. K., Unutmaz, D. (2005). Transcription factor GATA-1 potently represses the expression of the HIV-1 coreceptor CCR5 in human T cells and dendritic cells. Blood 106: 3440-3448 [Abstract] [Full Text]  
• Terwey, T. H., Kim, T. D., Kochman, A. A., Hubbard, V. M., Lu, S., Zakrzewski, J. L., Ramirez-Montagut, T., Eng, J. M., Muriglan, S. J., Heller, G., Murphy, G. F., Liu, C., Budak-Alpdogan, T., Alpdogan, O., van den Brink, M. R. M. (2005). CCR2 is required for CD8-induced graft-versus-host disease. Blood 106: 3322-3330 [Abstract] [Full Text]  
• Kouroumalis, A., Nibbs, R. J., Aptel, H., Wright, K. L., Kolios, G., Ward, S. G. (2005). The Chemokines CXCL9, CXCL10, and CXCL11 Differentially Stimulate G{alpha}i-Independent Signaling and Actin Responses in Human Intestinal Myofibroblasts. J. Immunol. 175: 5403-5411 [Abstract] [Full Text]  
• Rimoldi, M., Chieppa, M., Larghi, P., Vulcano, M., Allavena, P., Rescigno, M. (2005). Monocyte-derived dendritic cells activated by bacteria or by bacteria-stimulated epithelial cells are functionally different. Blood 106: 2818-2826 [Abstract] [Full Text]  
• Takeuchi, A., Usui, Y., Takeuchi, M., Hattori, T., Kezuka, T., Suzuki, J., Okunuki, Y., Iwasaki, T., Haino, M., Matsushima, K., Usui, M. (2005). CCR5-Deficient Mice Develop Experimental Autoimmune Uveoretinitis in the Context of a Deviant Effector Response. IOVS 46: 3753-3760 [Abstract] [Full Text]  
• Bendriss-Vermare, N., Burg, S., Kanzler, H., Chaperot, L., Duhen, T., de Bouteiller, O., D'agostini, M., Bridon, J.-M., Durand, I., Sederstrom, J. M., Chen, W., Plumas, J., Jacob, M.-C., Liu, Y.-J., Garrone, P., Trinchieri, G., Caux, C., Briere, F. (2005). Virus overrides the propensity of human CD40L-activated plasmacytoid dendritic cells to produce Th2 mediators through synergistic induction of IFN-{gamma} and Th1 chemokine production. J. Leukoc. Biol. 78: 954-966 [Abstract] [Full Text]  
• Morimoto, Y., Bian, Y., Gao, P., Yashiro-Ohtani, Y., Zhou, X.-Y., Ono, S., Nakahara, H., Kogo, M., Hamaoka, T., Fujiwara, H. (2005). Induction of surface CCR4 and its functionality in mouse Th2 cells is regulated differently during Th2 development. J. Leukoc. Biol. 78: 753-761 [Abstract] [Full Text]  
• Zaunders, J. J., Munier, M. L., Kaufmann, D. E., Ip, S., Grey, P., Smith, D., Ramacciotti, T., Quan, D., Finlayson, R., Kaldor, J., Rosenberg, E. S., Walker, B. D., Cooper, D. A., Kelleher, A. D., on behalf of the PHAEDRA Study Team, (2005). Early proliferation of CCR5+ CD38+++ antigen-specific CD4+ Th1 effector cells during primary HIV-1 infection. Blood 106: 1660-1667 [Abstract] [Full Text]  
• Yoo, J., Omori, M., Gyarmati, D., Zhou, B., Aye, T., Brewer, A., Comeau, M. R., Campbell, D. J., Ziegler, S. F. (2005). Spontaneous atopic dermatitis in mice expressing an inducible thymic stromal lymphopoietin transgene specifically in the skin. J. Exp. Med. 202: 541-549 [Abstract] [Full Text]  
• Chakravarti, S., Sabatos, C. A., Xiao, S., Illes, Z., Cha, E. K., Sobel, R. A., Zheng, X. X., Strom, T. B., Kuchroo, V. K. (2005). Tim-2 regulates T helper type 2 responses and autoimmunity. J. Exp. Med. 202: 437-444 [Abstract] [Full Text]  
• Dardalhon, V., Schubart, A. S., Reddy, J., Meyers, J. H., Monney, L., Sabatos, C. A., Ahuja, R., Nguyen, K., Freeman, G. J., Greenfield, E. A., Sobel, R. A., Kuchroo, V. K. (2005). CD226 Is Specifically Expressed on the Surface of Th1 Cells and Regulates Their Expansion and Effector Functions. J. Immunol. 175: 1558-1565 [Abstract] [Full Text]  
• Robertson, M. J., Chang, H.-C., Pelloso, D., Kaplan, M. H. (2005). Impaired interferon-{gamma} production as a consequence of STAT4 deficiency after autologous hematopoietic stem cell transplantation for lymphoma. Blood 106: 963-970 [Abstract] [Full Text]  
• Guerau-de-Arellano, M., Alroy, J., Huber, B. T. (2005). {beta}2 Integrins Control the Severity of Murine Lyme Carditis. Infect. Immun. 73: 3242-3250 [Abstract] [Full Text]  
• Wysocki, C. A., Panoskaltsis-Mortari, A., Blazar, B. R., Serody, J. S. (2005). Leukocyte migration and graft-versus-host disease. Blood 105: 4191-4199 [Abstract] [Full Text]  
• Mo, R., Chen, J., Grolleau-Julius, A., Murphy, H. S., Richardson, B. C., Yung, R. L. (2005). Estrogen Regulates CCR Gene Expression and Function in T Lymphocytes. J. Immunol. 174: 6023-6029 [Abstract] [Full Text]  
• Wang, J., Alvarez, R., Roderiquez, G., Guan, E., Caldwell, Q., Wang, J., Phelan, M., Norcross, M. A. (2005). CpG-Independent Synergistic Induction of {beta}-Chemokines and a Dendritic Cell Phenotype by Orthophosphorothioate Oligodeoxynucleotides and Granulocyte-Macrophage Colony-Stimulating Factor in Elutriated Human Primary Monocytes. J. Immunol. 174: 6113-6121 [Abstract] [Full Text]  

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