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*
Laboratory of Clinical Investigation and
Flow Cytometry Unit, Office of the Scientific Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
To address the issues of redundancy and specificity of chemokines and their receptors in lymphocyte biology, we investigated the expression of CC chemokine receptors CCR1, CCR2, CCR3, CCR5, CXCR3, and CXCR4 and responses to their ligands on memory and naive, CD4 and CD8 human T cells, both freshly isolated and after short term activation in vitro. Activation through CD3 for 3 days had the most dramatic effects on the expression of CXCR3, which was up-regulated and functional on all T cell populations including naive CD4 cells. In contrast, the effects of short term activation on expression of other chemokine receptors was modest, and expression of CCR2, CCR3, and CCR5 on CD4 cells was restricted to memory subsets. In general, patterns of chemotaxis in the resting cells and calcium responses in the activated cells corresponded to the patterns of receptor expression among T cell subsets. In contrast, the pattern of calcium signaling among subsets of freshly isolated cells did not show a simple correlation with receptor expression, so the propensity to produce a global rise in the intracellular calcium concentration differed among the various receptors within a given T cell subset and for an individual receptor depending on the cell where it was expressed. Our data suggest that individual chemokine receptors and their ligands function on T cells at different stages of T cell activation/differentiation, with CXCR3 of particular importance on newly activated cells, and demonstrate T cell subset-specific and activation state-specific responses to chemokines that are achieved by regulating receptor signaling as well as receptor expression.
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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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P. Romagnani, F. Annunziato, E. Lazzeri, L. Cosmi, C. Beltrame, L. Lasagni, G. Galli, M. Francalanci, R. Manetti, F. Marra, et al. Interferon-inducible protein 10, monokine induced by interferon gamma, and interferon-inducible T-cell alpha chemoattractant are produced by thymic epithelial cells and attract T-cell receptor (TCR) {alpha}{beta}+CD8+ single-positive T cells, TCR{gamma}{delta}+ T cells, and natural killer-type cells in human thymus Blood, February 1, 2001; 97(3): 601 - 607. [Abstract] [Full Text] [PDF]
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C. Voermans, M. L. K. Kooi, S. Rodenhuis, H. van der Lelie, C. E. van der Schoot, and W. R. Gerritsen In vitro migratory capacity of CD34+ cells is related to hematopoietic recovery after autologous stem cell transplantation Blood, February 1, 2001; 97(3): 799 - 804. [Abstract] [Full Text] [PDF]
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S. S. Cheng, J. J. Lai, N. W. Lukacs, and S. L. Kunkel Granulocyte-Macrophage Colony Stimulating Factor Up-Regulates CCR1 in Human Neutrophils J. Immunol., January 15, 2001; 166(2): 1178 - 1184. [Abstract] [Full Text] [PDF]
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M. Inngjerdingen, B. Damaj, and A. A. Maghazachi Expression and regulation of chemokine receptors in human natural killer cells Blood, January 15, 2001; 97(2): 367 - 375. [Abstract] [Full Text] [PDF]
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L. Kremer, L. Carramolino, I. Goya, A. Zaballos, J. Gutierrez, M. del Carmen Moreno-Ortiz, C. Martinez-A., and G. Marquez The Transient Expression of C-C Chemokine Receptor 8 in Thymus Identifies a Thymocyte Subset Committed to Become CD4+ Single-Positive T Cells J. Immunol., January 1, 2001; 166(1): 218 - 225. [Abstract] [Full Text] [PDF]
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 S. SEGERER, Y. CUI, K. L. HUDKINS, T. GOODPASTER, F. EITNER, M. MACK, D. SCHLÖNDORFF, and C. E. ALPERS Expression of the Chemokine Monocyte Chemoattractant Protein-1 and Its Receptor Chemokine Receptor 2 in Human Crescentic Glomerulonephritis J. Am. Soc. Nephrol., December 1, 2000; 11(12): 2231 - 2242. [Abstract] [Full Text]
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C. AGOSTINI, M. FACCO, M. SIVIERO, D. CAROLLO, S. GALVAN, A. M. CATTELAN, R. ZAMBELLO, L. TRENTIN, and G. SEMENZATO CXC Chemokines IP-10 and Mig Expression and Direct Migration of Pulmonary CD8+/CXCR3+ T Cells in the Lungs of Patients with HIV Infection and T-Cell Alveolitis Am. J. Respir. Crit. Care Med., October 1, 2000; 162(4): 1466 - 1473. [Abstract] [Full Text] [PDF]
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R. Krzysiek, E. A. Lefevre, J. Bernard, A. Foussat, P. Galanaud, F. Louache, and Y. Richard Regulation of CCR6 chemokine receptor expression and responsiveness to macrophage inflammatory protein-3alpha /CCL20 in human B cells Blood, October 1, 2000; 96(7): 2338 - 2345. [Abstract] [Full Text] [PDF]
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D. Unutmaz, W. Xiang, M. J. Sunshine, J. Campbell, E. Butcher, and D. R. Littman The Primate Lentiviral Receptor Bonzo/STRL33 Is Coordinately Regulated with CCR5 and Its Expression Pattern Is Conserved Between Human and Mouse J. Immunol., September 15, 2000; 165(6): 3284 - 3292. [Abstract] [Full Text] [PDF]
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T. Pierson, T. L. Hoffman, J. Blankson, D. Finzi, K. Chadwick, J. B. Margolick, C. Buck, J. D. Siliciano, R. W. Doms, and R. F. Siliciano Characterization of Chemokine Receptor Utilization of Viruses in the Latent Reservoir for Human Immunodeficiency Virus Type 1 J. Virol., September 1, 2000; 74(17): 7824 - 7833. [Abstract] [Full Text]
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R. Maier, M. M. Bartolome-Rodriguez, C. Moulon, H. U. Weltzien, and A. Meyerhans Kinetics of CXCR4 and CCR5 up-regulation and human immunodeficiency virus expansion after antigenic stimulation of primary CD4+ T lymphocytes Blood, September 1, 2000; 96(5): 1853 - 1856. [Abstract] [Full Text] [PDF]
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J. Arthos, A. Rubbert, R. L. Rabin, C. Cicala, E. Machado, K. Wildt, M. Hanbach, T. D. Steenbeke, R. Swofford, J. M. Farber, et al. CCR5 Signal Transduction in Macrophages by Human Immunodeficiency Virus and Simian Immunodeficiency Virus Envelopes J. Virol., July 15, 2000; 74(14): 6418 - 6424. [Abstract] [Full Text]
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M. Inngjerdingen, B. Damaj, and A. A. Maghazachi Human NK Cells Express CC Chemokine Receptors 4 and 8 and Respond to Thymus and Activation-Regulated Chemokine, Macrophage-Derived Chemokine, and I-309 J. Immunol., April 15, 2000; 164(8): 4048 - 4054. [Abstract] [Full Text] [PDF]
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H. Kojima, M. Toda, and M. V. Sitkovsky Comparison of Fas- versus perforin-mediated pathways of cytotoxicity in TCR- and Thy-1-activated murine T cells Int. Immunol., March 1, 2000; 12(3): 365 - 374. [Abstract] [Full Text] [PDF]
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 P. M. Murphy, M. Baggiolini, I. F. Charo, C. A. Hebert, R. Horuk, K. Matsushima, L. H. Miller, J. J. Oppenheim, and C. A. Power International Union of Pharmacology. XXII. Nomenclature for Chemokine Receptors Pharmacol. Rev., March 1, 2000; 52(1): 145 - 176. [Abstract] [Full Text] [PDF]
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C.-R. Yu, K. W. C. Peden, M. B. Zaitseva, H. Golding, and J. M. Farber CCR9A and CCR9B: Two Receptors for the Chemokine CCL25/TECK/Ck{beta}-15 That Differ in Their Sensitivities to Ligand J. Immunol., February 1, 2000; 164(3): 1293 - 1305. [Abstract] [Full Text] [PDF]
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A. Trkola, J. Matthews, C. Gordon, T. Ketas, and J. P. Moore A Cell Line-Based Neutralization Assay for Primary Human Immunodeficiency Virus Type 1 Isolates That Use either the CCR5 or the CXCR4 Coreceptor J. Virol., November 1, 1999; 73(11): 8966 - 8974. [Abstract] [Full Text] [PDF]
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M. Honczarenko, R. S. Douglas, C. Mathias, B. Lee, M. Z. Ratajczak, and L. E. Silberstein SDF-1 Responsiveness Does Not Correlate With CXCR4 Expression Levels of Developing Human Bone Marrow B Cells Blood, November 1, 1999; 94(9): 2990 - 2998. [Abstract] [Full Text] [PDF]
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 A. Motsinger, D. W. Haas, A. K. Stanic, L. Van Kaer, S. Joyce, and D. Unutmaz CD1d-restricted Human Natural Killer T Cells Are Highly Susceptible to Human Immunodeficiency Virus 1 Infection J. Exp. Med., April 1, 2002; 195(7): 869 - 879. [Abstract] [Full Text] [PDF]
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