J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/02/573/06 $2.00
Volume 185 February 1997 573-578

BRIEF DEFINITIVE REPORT:
P-Selectin Glycoprotein Ligand-1 (PSGL-1) on T Helper 1 but Not on T Helper 2 Cells Binds to P-Selectin and Supports Migration into Inflamed Skin

By Eric Borges,^* Wolfgang Tietz, Martin Steegmaier,^* Thomas Moll,^* Rupert Hallmann,^§ Alf Hamann, and Dietmar Vestweber^*

From the ^* Institut für Zellbiologie, ZMBE, Universität Münster, Germany;  Abteilung für Immunologie, Medizinische Klinik, Universitätskrankenhaus Eppendorf, Hamburg, Germany; ^§ Institut für Exp. Medizin u. Bindegewebsforschung, Universität Erlangen-Nürnberg, Germany

We have shown recently that mouse Th1 cells but not Th2 cells are selectively recruited into inflamed sites of a delayed-type hypersensitivity (DTH) reaction of the skin. This migration was blocked by monoclonal antibodies (mAb) against P- and E-selectin. Here we show that Th1 cells bind to P-selectin via the P-selectin glycoprotein ligand-1 (PSGL-1). This is the only glycoprotein ligand that was detectable by affinity isolation with a P-selectin-Ig fusion protein. Binding of Th1 cells to P-selectin, as analyzed by flow cytometry and in cell adhesion assays, was completely blocked by antibodies against PSGL-1. The same antibodies blocked partially the migration of Th1 cells into cutaneous DTH reactions. This blocking activity, in combination with that of a mAb against E-selectin, was additive. PSGL-1 on Th2 cells, although expressed at similar levels as on Th1 cells, did not support binding to P-selectin. Thus, the P-selectin-binding form of PSGL-1 distinguishes Th1 cells from Th2 cells. Furthermore, PSGL-1 is relevant for the entry of Th1 cells into inflamed areas of the skin. This is the first demonstration for the importance of PSGL-1 for mouse leukocyte recruitment in vivo.

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• Xie, H., Lim, Y.-C., Luscinskas, F. W., Lichtman, A. H. (1999). Acquisition of Selectin Binding and Peripheral Homing Properties by CD4+ and CD8+ T Cells. J. Exp. Med. 189: 1765-1776 [Abstract] [Full Text]  
• Suzuki, N., Nakajima, A., Yoshino, S., Matsushima, K., Yagita, H., Okumura, K. (1999). Selective accumulation of CCR5+ T lymphocytes into inflamed joints of rheumatoid arthritis. Int Immunol 11: 553-559 [Abstract] [Full Text]  
• Lim, Y.-C., Henault, L., Wagers, A. J., Kansas, G. S., Luscinskas, F. W., Lichtman, A. H. (1999). Expression of Functional Selectin Ligands on Th Cells Is Differentially Regulated by IL-12 and IL-4. J. Immunol. 162: 3193-3201 [Abstract] [Full Text]  
• McHale, J. F., Harari, O. A., Marshall, D., Haskard, D. O. (1999). Vascular Endothelial Cell Expression of ICAM-1 and VCAM-1 at the Onset of Eliciting Contact Hypersensitivity in Mice: Evidence for a Dominant Role of TNF-{alpha}. J. Immunol. 162: 1648-1655 [Abstract] [Full Text]  
• Morgan, S. M., Samulowitz, U., Darley, L., Simmons, D. L., Vestweber, D. (1999). Biochemical Characterization and Molecular Cloning of a Novel Endothelial-Specific Sialomucin. Blood 93: 165-175 [Abstract] [Full Text]  
• Wagers, A. J., Waters, C. M., Stoolman, L. M., Kansas, G. S. (1998). Interleukin 12 and Interleukin 4 Control T Cell Adhesion to Endothelial Selectins through Opposite Effects on alpha 1,3-fucosyltransferase VII Gene Expression. J. Exp. Med. 188: 2225-2231 [Abstract] [Full Text]  
• Wolber, F. M., Curtis, J. L., Maly, P., Kelly, R. J., Smith, P., Yednock, T. A., Lowe, J. B., Stoolman, L. M. (1998). Endothelial Selectins and {alpha}4 Integrins Regulate Independent Pathways of T Lymphocyte Recruitment in the Pulmonary Immune Response. J. Immunol. 161: 4396-4403 [Abstract] [Full Text]  
• Kaplan, M. H., Wurster, A. L., Grusby, M. J. (1998). A Signal Transducer and Activator of  Transcription (Stat)4-independent Pathway for the Development of  T Helper Type 1 Cells. J. Exp. Med. 188: 1191-1196 [Abstract] [Full Text]  
• Guerder, S., Eynon, E. E., Flavell, R. A. (1998). Autoimmunity Without Diabetes in Transgenic Mice Expressing {beta} Cell-Specific CD86, But Not CD80: Parameters that Trigger Progression to Diabetes. J. Immunol. 161: 2128-2140 [Abstract] [Full Text]  
• Teixeira, M. M., Hellewell, P. G. (1998). Contribution of Endothelial Selectins and {alpha}4 Integrins to Eosinophil Trafficking in Allergic and Nonallergic Inflammatory Reactions in Skin. J. Immunol. 161: 2516-2523 [Abstract] [Full Text]  
• Yago, T., Tsukuda, M., Fukushima, H., Yamaoka, H., Kurata-Miura, K., Nishi, T., Minami, M. (1998). IL-12 Promotes the Adhesion of NK Cells to Endothelial Selectins Under Flow Conditions. J. Immunol. 161: 1140-1145 [Abstract] [Full Text]  
• Tietz, W., Allemand, Y., Borges, E., von Laer, D., Hallmann, R., Vestweber, D., Hamann, A. (1998). CD4+ T Cells Migrate into Inflamed Skin Only If They Express Ligands for E- and P-Selectin. J. Immunol. 161: 963-970 [Abstract] [Full Text]  
• Massberg, S., Enders, G., Leiderer, R., Eisenmenger, S., Vestweber, D., Krombach, F., Messmer, K. (1998). Platelet-Endothelial Cell Interactions During Ischemia/Reperfusion: The Role of P-Selectin. Blood 92: 507-515 [Abstract] [Full Text]  
• Steinhoff, U., Klemm, U., Greiner, M., Bordasch, K., Kaufmann, S. H. E. (1998). Altered Intestinal Immune System but Normal Antibacterial Resistance in the Absence of P-Selectin and ICAM-1. J. Immunol. 160: 6112-6120 [Abstract] [Full Text]  
• Salmi, M., Hellman, J., Jalkanen, S. (1998). The Role of Two Distinct Endothelial Molecules, Vascular Adhesion Protein-1 and Peripheral Lymph Node Addressin, in the Binding of Lymphocyte Subsets to Human Lymph Nodes. J. Immunol. 160: 5629-5636 [Abstract] [Full Text]  
• Cines, D. B., Pollak, E. S., Buck, C. A., Loscalzo, J., Zimmerman, G. A., McEver, R. P., Pober, J. S., Wick, T. M., Konkle, B. A., Schwartz, B. S., Barnathan, E. S., McCrae, K. R., Hug, B. A., Schmidt, A.-M., Stern, D. M. (1998). Endothelial Cells in Physiology and in the Pathophysiology of Vascular Disorders. Blood 91: 3527-3561 [Full Text]  
• Sallusto, F., Lenig, D., Mackay, C. R., Lanzavecchia, A. (1998). Flexible Programs of Chemokine Receptor Expression on Human Polarized T Helper 1 and 2 Lymphocytes. J. Exp. Med. 187: 875-883 [Abstract] [Full Text]  
• Engelhardt, B., Vestweber, D., Hallmann, R., Schulz, M. (1997). E- and P-Selectin Are Not Involved in the Recruitment of Inflammatory Cells Across the Blood-Brain Barrier in Experimental Autoimmune Encephalomyelitis. Blood 90: 4459-4472 [Abstract] [Full Text]  

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