Homing and cellular traffic in lymph nodes (original) (raw)

• Gowans, J. L. & Knight, E. J. The route of re-circulation of lymphocytes in the rat. Proc. R. Soc. Lond. B 159, 257–282 (1964). A classic study that provided the first clear experimental evidence for lymphocyte recirculation from blood to lymph nodes (LNs) and through the thoracic duct, back to the blood.
  Article CAS PubMed Google Scholar
• Marchesi, V. T. & Gowans, J. L. The migration of lymphocytes through the endothelium of venules in lymph nodes: an electron microscope study. Proc. R. Soc. B 159, 283–290 (1964).
  Article CAS Google Scholar
• Girard, J. -P. & Springer, T. A. High endothelial venules (HEVs): Specialized endothelium for lymphocyte migration. Immunol. Today 16, 449–457 (1995).
  Article CAS PubMed Google Scholar
• Pabst, R. The spleen in lymphocyte migration. Immunol. Today 9, 43–45 (1988).
  Article CAS PubMed Google Scholar
• Gesner, B. M. & Gowans, J. L. The output of lymphocytes from the thoracic duct of unanaesthetized mice. Br. J. Exp. Path. 43, 424 (1962).
  CAS Google Scholar
• Scheinecker, C., McHugh, R., Shevach, E. M. & Germain, R. N. Constitutive presentation of a natural tissue autoantigen exclusively by dendritic cells in the draining lymph node. J. Exp. Med. 196, 1079–1090 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Butcher, E. C. & Picker, L. J. Lymphocyte homing and homeostasis. Science 272, 60–66 (1996).
  Article CAS PubMed Google Scholar
• von Andrian, U. H. & Mackay, C. R. T-cell function and migration. Two sides of the same coin. N. Engl. J. Med. 343, 1020–1034 (2000).
  Article CAS PubMed Google Scholar
• Kantele, A., Westerholm, M., Kantele, J. M., Makela, P. H. & Savilahti, E. Homing potentials of circulating antibody-secreting cells after administration of oral or parenteral protein or polysaccharide vaccine in humans. Vaccine 17, 229–236 (1999).
  Article CAS PubMed Google Scholar
• Kantele, A., Zivny, J., Hakkinen, M., Elson, C. O. & Mestecky, J. Differential homing commitments of antigen-specific T cells after oral or parenteral immunization in humans. J. Immunol. 162, 5173–5177 (1999).
  CAS PubMed Google Scholar
• Campbell, D. J. & Butcher, E. C. Rapid acquisition of tissue-specific homing phenotypes by CD4+ T cells activated in cutaneous or mucosal lymphoid tissues. J. Exp. Med. 195, 135–141 (2002). This study shows that intraperitoneal injection of a model antigen rapidly induces antigen-specific effector cells in peripheral LNs and gut-associated lymphoid tissues, which have a skin-homing and gut-homing phenotype, respectively.
  Article CAS PubMed PubMed Central Google Scholar
• Stagg, A. J., Kamm, M. A. & Knight, S. C. Intestinal dendritic cells increase T cell expression of α4β7 integrin. Eur. J. Immunol. 32, 1445–1454 (2002).
  Article CAS PubMed Google Scholar
• Mora, J. R. et al. Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells. Nature 424, 88–93 (2003).
  Article CAS PubMed Google Scholar
• Sallusto, F., Lenig, D., Forster, R., Lipp, M. & Lanzavecchia, A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401, 708–712 (1999). This study shows that memory T cells can be subdivided into CC-chemokine receptor 7 (CCR7)+L-selectin+ central memory cells and CCR7 − L-selectin − effector memory cells, which show distinct responses to recall antigens.
  Article CAS PubMed Google Scholar
• Weninger, W., Crowley, M. A., Manjunath, N. & von Andrian, U. H. Migratory properties of naive, effector, and memory CD8+ T cells. J. Exp. Med. 194, 953–966 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Manjunath, N. et al. Effector differentiation is not prerequisite for generation of memory cytotoxic T lymphocytes. J. Clin. Invest. 108, 871–878 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Mondino, A., Khoruts, A. & Jenkins, M. K. The anatomy of T-cell activation and tolerance. Proc. Natl Acad. Sci. USA 93, 2245–2252 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Fossum, S. & Ford, W. L. The organization of cell populations within lymph nodes: their origin, life history and functional relationships. Histopathology 9, 469–499 (1985).
  Article CAS PubMed Google Scholar
• Pabst, R. & Binns, R. M. Heterogeneity of lymphocyte homing physiology: several mechanisms operate in the control of migration to lymphoid and non-lymphoid organs in vivo. Immunol. Rev. 108, 83–109 (1989).
  Article CAS PubMed Google Scholar
• Sainte-Marie, G. & Peng, F. S. High endothelial venules of the rat lymph node. A review and a question: is their activity antigen specific? Anat. Rec. 245, 593–620 (1996).
  Article CAS PubMed Google Scholar
• Gretz, J. E., Anderson, A. O. & Shaw, S. Cords, channels, corridors and conduits: critical architectural elements facilitating cell interactions in the lymph node cortex. Immunol. Rev. 156, 11–24 (1997).
  Article CAS PubMed Google Scholar
• Kelly, R. H. Functional anatomy of lymph nodes. I. The paracortical cords. Int. Arch. Allergy Appl. Immunol. 48, 836–849 (1975).
  Article CAS PubMed Google Scholar
• von Andrian, U. H. Intravital microscopy of the peripheral lymph node microcirculation in mice. Microcirc. 3, 287–300 (1996).
  Article CAS Google Scholar
• M'Rini, C. et al. A novel endothelial L-selectin ligand activity in lymph node medulla that is regulated by α(1,3)-fucosyltransferase-IV. J. Exp. Med. (in the press).
• Mebius, R. E., Streeter, P. R., Michie, S., Butcher, E. C. & Weissman, I. L. A developmental switch in lymphocyte homing receptor and endothelial vascular addressin expression regulates lymphocyte homing and permits CD4+CD3− cells to colonize lymph nodes. Proc. Natl Acad. Sci. USA 93, 11019–11024 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Hendriks, H. R., Eestermans, I. L. & Hoefsmit, E. C. Depletion of macrophages and disappearance of postcapillary high endothelial venules in lymph nodes deprived of afferent lymphatic vessels. Cell Tissue Res. 211, 375–389 (1980).
  Article CAS PubMed Google Scholar
• Hendriks, H. R., Duijvestijn, A. M. & Kraal, G. Rapid decrease in lymphocyte adherence to high endothelial venules in lymph nodes deprived of afferent lymphatic vessels. Eur. J. Immunol. 17, 1691–1695 (1987).
  Article CAS PubMed Google Scholar
• Mebius, R. E., Bauer, J., Agaath, J. T. T., Brevé, J. & Kraal, G. The functional activity of high endothelial venules: a role for the subcapsular sinus macrophages in the lymph node. Immunobiology 182, 277–291 (1991).
  Article CAS PubMed Google Scholar
• Hendriks, H. R., von Hemert, N. A. & van der Heijden, M. The effect of stimulated macrophages on high endothelial venules and germinal centres in lymph nodes of rat. Adv. Exp. Med. Biol. 149, 207–212 (1982).
  Article CAS PubMed Google Scholar
• Mebius, R. E., Streeter, P. R., Breve, J., Duijvestijn, A. M. & Kraal, G. The influence of afferent lymphatic vessel interruption on vascular addressin expression. J. Cell Biol. 115, 85–95 (1991).
  Article CAS PubMed Google Scholar
• Kratz, A., Campos-Neto, A., Hanson, M. S. & Ruddle, N. H. Chronic inflammation caused by lymphotoxin is lymphoid neogenesis. J. Exp. Med. 183, 1461–1472 (1996).
  Article CAS PubMed Google Scholar
• Fan, L., Reilly, C. R., Luo, Y., Dorf, M. E. & Lo, D. Cutting edge: ectopic expression of the chemokine TCA4/SLC is sufficient to trigger lymphoid neogenesis. J. Immunol. 164, 3955–3959 (2000).
  Article CAS PubMed Google Scholar
• Luther, S. A. et al. Differing activities of homeostatic chemokines CCL19, CCL21, and CXCL12 in lymphocyte and dendritic cell recruitment and lymphoid neogenesis. J. Immunol. 169, 424–433 (2002).
  Article CAS PubMed Google Scholar
• Chen, S. C. et al. Ectopic expression of the murine chemokines CCL21a and CCL21b induces the formation of lymph node-like structures in pancreas, but not skin, of transgenic mice. J. Immunol. 168, 1001–1008 (2002).
  Article CAS PubMed Google Scholar
• Schrama, D. et al. Targeting of lymphotoxin-α to the tumor elicits an efficient immune response associated with induction of peripheral lymphoid-like tissue. Immunity 14, 111–121 (2001).
  Article CAS PubMed Google Scholar
• De Togni, P. et al. Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science 264, 703–707 (1994).
  Article CAS PubMed Google Scholar
• Koni, P. A. et al. Distinct roles in lymphoid organogenesis for lymphotoxins α and β revealed in lymphotoxin β-deficient mice. Immunity 6, 491–500 (1997).
  Article CAS PubMed Google Scholar
• Uccini, S. et al. Kaposi's sarcoma cells express the macrophage-associated antigen mannose receptor and develop in peripheral blood cultures of Kaposi's sarcoma patients. Am. J. Pathol. 150, 929–938 (1997).
  CAS PubMed PubMed Central Google Scholar
• Irjala, H. et al. Mannose receptor is a novel ligand for L-selectin and mediates lymphocyte binding to lymphatic endothelium. J. Exp. Med. 194, 1033–1042 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Ingulli, E., Ulman, D. R., Lucido, M. M. & Jenkins, M. K. In situ analysis reveals physical interactions between CD11b+ dendritic cells and antigen-specific CD4+ T cells after subcutaneous injection of antigen. J. Immunol. 169, 2247–2252 (2002).
  Article CAS PubMed Google Scholar
• Gretz, J. E., Norbury, C. C., Anderson, A. O., Proudfoot, A. E. & Shaw, S. Lymph-borne chemokines and other low molecular weight molecules reach high endothelial venules via specialized conduits while a functional barrier limits access to the lymphocyte microenvironments in lymph node cortex. J. Exp. Med. 192, 1425–1440 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Anderson, A. O. & Shaw, S. T cell adhesion to endothelium: the FRC conduit system and other anatomic and molecular features which facilitate the adhesion cascade in lymph node. Semin. Immunol. 5, 271–282 (1993).
  Article CAS PubMed Google Scholar
• Stein, J. V. et al. The CC chemokine thymus-derived chemotactic agent 4 (TCA-4, secondary lymphoid tissue chemokine, 6Ckine, exodus-2) triggers lymphocyte function-associated antigen 1-mediated arrest of rolling T lymphocytes in peripheral lymph node high endothelial venules. J. Exp. Med. 191, 61–76 (2000). Intravital microscopy was used to show that CC-chemokine ligand 21 (CCL21) induces the activation of leukocyte function-associated antigen 1 (LFA1) on rolling naive T cells in LN high endothelial venules (HEVs). This paper also shows that a chemokine can be transported from the skin to the draining LNs and presented in HEVs.
  Article CAS PubMed PubMed Central Google Scholar
• Baekkevold, E. S. et al. The CCR7 ligand ELC (CCL19) is transcytosed in high endothelial venules and mediates T cell recruitment. J. Exp. Med. 193, 1105–1112 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Palframan, R. T. et al. Inflammatory chemokine transport and presentation in HEV: A remote control mechanism for monocyte recruitment to lymph nodes in inflamed tissues. J. Exp. Med. 194, 1361–1374 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Hawiger, D. et al. Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J. Exp. Med. 194, 769–779 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Titball, R. W. & Leary, S. E. Plague. Br. Med. Bull. 54, 625–633 (1998).
  Article CAS PubMed Google Scholar
• Smith, J. & Reisner, B. in Pathology of infectious diseases (ed. Connor, D. H.) 729–738 (Appleton and Lange, Stamford, 1997).
  Google Scholar
• Cloyd, M. W., Chen, J. J. & Wang, I. How does HIV cause AIDS? The homing theory. Mol. Med. Today 6, 108–111 (2000).
  Article CAS PubMed Google Scholar
• Mock, M. & Fouet, A. Anthrax. Annu. Rev. Microbiol. 55, 647–671 (2001).
  Article CAS PubMed Google Scholar
• Mackay, C. R., Marston, W. L. & Dudler, L. Naive and memory T cells show distinct pathways of lymphocyte recirculation. J. Exp. Med. 171, 801–817 (1990). This study shows that afferent lymph contains memory but not naive T cells, indicating that the latter can only home to LNs through HEVs, whereas (a subset of) the former migrate through peripheral tissues.
  Article CAS PubMed Google Scholar
• Cahill, R. N. P., Frost, H. & Trnka, Z. The effects of antigen on the migration of recirculating lymphocytes through single lymph nodes. J. Exp. Med. 143, 870–888 (1976).
  Article CAS PubMed Google Scholar
• Ford, W. L., Simmonds, S. J. & Atkins, R. C. Early cellular events in a systemic graft-vs-host reaction. II. Autoradiographic estimates of the frequency of donor lymphocytes which respond to each Ag-B-determined antigenic complex. J. Exp. Med. 141, 681–696 (1975).
  Article CAS PubMed Google Scholar
• Mackay, C. R., Marston, W. & Dudler, L. Altered patterns of T cell migration through lymph nodes and skin following antigen challenge. Eur. J. Immunol. 22, 2205–2210 (1992).
  Article CAS PubMed Google Scholar
• Springer, T. A. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multi-step paradigm. Cell 76, 301–314 (1994).
  Article CAS PubMed Google Scholar
• Warnock, R. A., Askari, S., Butcher, E. C. & von Andrian, U. H. Molecular mechanisms of lymphocyte homing to peripheral lymph nodes. J. Exp. Med. 187, 205–216 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Okada, T. et al. Chemokine requirements for B cell entry to lymph nodes and Peyer's patches. J. Exp. Med. 196, 65–75 (2002). This study shows that both CCR7 and CXC-chemokine receptor 4 (CXCR4) transmit integrin-activating signals in rolling B cells in LN HEVs.
  Article CAS PubMed PubMed Central Google Scholar
• Streeter, P. R., Rouse, B. T. N. & Butcher, E. C. Immunohistologic and functional characterization of a vascular addressin involved in lymphocyte homing into peripheral lymph nodes. J. Cell Biol. 107, 1853–1862 (1988).
  Article CAS PubMed Google Scholar
• Berg, E. L., Robinson, M. K., Warnock, R. A. & Butcher, E. C. The human peripheral lymph node vascular addressin is a ligand for LECAM-1, the peripheral lymph node homing receptor. J. Cell Biol. 114, 343–349 (1991).
  Article CAS PubMed Google Scholar
• Clark, R. A., Fuhlbrigge, R. C. & Springer, T. A. L-selectin ligands that are O-glycoprotease-resistant and distinct from MECA-79 antigen are sufficient for tethering and rolling of lymphocytes on human high endothelial venules. J. Cell Biol. 140, 721–731 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Lowe, J. B. Glycosylation, immunity, and autoimmunity. Cell 104, 809–812 (2001).
  Article CAS PubMed Google Scholar
• Vestweber, D. & Blanks, J. E. Mechanisms that regulate the function of the selectins and their ligands. Physiol. Rev. 79, 181–213 (1999).
  Article CAS PubMed Google Scholar
• Hamann, A. et al. Evidence for an accessory role of LFA-1 in lymphocyte-high endothelium interaction during homing. J. Immunol. 140, 693–699 (1988).
  CAS PubMed Google Scholar
• Andrew, D. P. et al. Transendothelial migration and trafficking of leukocytes in LFA-1-deficient mice. Eur. J. Immunol. 28, 1959–1969 (1998).
  Article CAS PubMed Google Scholar
• Berlin-Rufenach, C. et al. Lymphocyte migration in lymphocyte function-associated antigen (LFA)-1-deficient mice. J. Exp. Med. 189, 1467–1478 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Gunn, M. D. et al. A chemokine expressed in lymphoid high endothelial venules promotes the adhesion and chemotaxis of naive T lymphocytes Proc. Natl Acad. Sci. USA. 95, 258–263 (1998). Using in situ hybridization, this study discovered that CCL21 is highly expressed by HEVs. CCL21 is also shown to be a potent chemoattractant for naive T cells.
  Article CAS PubMed PubMed Central Google Scholar
• Campbell, J. J. et al. Chemokines and the arrest of lymphoyctes rolling under flow conditions. Science 279, 381–384 (1998).
  Article CAS PubMed Google Scholar
• Campbell, J. J. et al. 6-C-kine (SLC), a lymphocyte adhesion-triggering chemokine expressed by high endothelium, is an agonist for the MIP-3β receptor CCR7. J. Cell Biol. 141, 1053–1059 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Vassileva, G. et al. The reduced expression of 6Ckine in the plt mouse results from the deletion of one of two 6Ckine genes. J. Exp. Med. 190, 1183–1188 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Nakano, H. & Gunn, M. D. Gene duplications at the chemokine locus on mouse chromosome 4: multiple strain-specific haplotypes and the deletion of secondary lymphoid-organ chemokine and EBI-1 ligand chemokine genes in the plt mutation. J. Immunol. 166, 361–369 (2001).
  Article CAS PubMed Google Scholar
• Forster, R. et al. CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell 99, 23–33 (1999). This study reports that CCR7-deficient mice have markedly disorganized secondary lymphoid tissues and are defective in lymphocyte homing.
  Article CAS PubMed Google Scholar
• Gunn, M. D. et al. Mice lacking expression of secondary lymphoid organ chemokine have defects in lymphocyte homing and dendritic cell localization. J. Exp. Med. 189, 451–460 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Cinamon, G., Shinder, V. & Alon, R. Shear forces promote lymphocyte migration across vascular endothelium bearing apical chemokines. Nature Immunol. 2, 515–522 (2001).
  Article CAS Google Scholar
• Weninger, W. et al. Naive T cell recruitment to non-lymphoid tissues: a role for endothelium-expressed CCL21 in autoimmune disease and lymphoid neogenesis. J. Immunol. 170, 4638–4648 (2003).
  Article CAS PubMed Google Scholar
• Tang, M. L., Steeber, D. A., Zhang, X. Q. & Tedder, T. F. Intrinsic differences in L-selectin expression levels affect T and B lymphocyte subset-specific recirculation pathways. J. Immunol. 160, 5113–5121 (1998).
  CAS PubMed Google Scholar
• Stein, J. V. et al. L-selectin-mediated leukocyte adhesion in vivo: microvillous distribution determines tethering efficiency, but not rolling velocity. J. Exp. Med. 189, 37–50 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Robert, C. et al. Gene therapy to target dendritic cells from blood to lymph nodes. Gene Therapy 10, 1479–1486 (2003).
  Article CAS PubMed Google Scholar
• Streeter, P. R., Lakey-Berg, E., Rouse, B. T. N., Bargatze, R. F. & Butcher, E. C. A tissue-specific endothelial cell molecule involved in lymphocyte homing. Nature 331, 41–46 (1988).
  Article CAS PubMed Google Scholar
• Berlin, C. et al. α4β7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell 74, 185–195 (1993).
  Article CAS PubMed Google Scholar
• Bargatze, R. F., Jutila, M. A. & Butcher, E. C. Distinct roles of L-selectin and integrins α4β7 and LFA-1 in lymphocyte homing to Peyer's patch-HEV in situ: The multistep model confirmed and refined. Immunity 3, 99–108 (1995).
  Article CAS PubMed Google Scholar
• Arbones, M. L. et al. Lymphocyte homing and leukocyte rolling and migration are impaired in L-selectin-deficient mice. Immunity 1, 247–260 (1994). The first detailed phenotypic characterization of L-selectin-deficient mice.
  Article CAS PubMed Google Scholar
• Wagner, N. et al. Critical role for β7 integrins in formation of the gut-associated lymphoid tissue. Nature 382, 366–370 (1996).
  Article CAS PubMed Google Scholar
• Kunkel, E. J. et al. The roles of L-selectin, β7 integrins, and P-selectin in leukocyte rolling and adhesion in high endothelial venules of Peyer's patches. J. Immunol. 161, 2449–2456 (1998).
  CAS PubMed Google Scholar
• Diacovo, T. G., Puri, K. D., Warnock, R. A., Springer, T. A. & von Andrian, U. H. Platelet-mediated lymphocyte delivery to high endothelial venules. Science 273, 252–255 (1996).
  Article CAS PubMed Google Scholar
• Salmi, M. & Jalkanen, S. VAP-1: an adhesin and an enzyme. Trends Immunol. 22, 211–216 (2001).
  Article CAS PubMed Google Scholar
• McEvoy, L. M., Sun, H., Frelinger, J. G. & Butcher, E. C. Anti-CD43 inhibition of T cell homing. J. Exp. Med. 185, 1493–1498 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Stockton, B. M., Cheng, G., Manjunath, N., Ardman, B. & von Andrian, U. H. Negative regulation of T cell homing by CD43. Immunity 8, 373–381 (1998).
  Article CAS PubMed Google Scholar
• Jalkanen, S. T., Bargatze, R. F., Herron, L. R. & Butcher, E. C. A lymphoid cell surface glycoprotein involved in endothelial cell recognition and lymphocyte homing in man. Eur. J. Immunol. 16, 1195–1202 (1986).
  Article CAS PubMed Google Scholar
• Stoop, R., Gal, I., Glant, T. T., McNeish, J. D. & Mikecz, K. Trafficking of CD44-deficient murine lymphocytes under normal and inflammatory conditions. Eur. J. Immunol. 32, 2532–2542 (2002).
  Article CAS PubMed Google Scholar
• Middleton, J. et al. Transcytosis and surface presentation of IL-8 by venular endothelial cells. Cell 91, 1001–1011 (1997). This study shows that extravascular chemokines can be transported in caveoli to the luminal surface of endothelial cells where they are presented to passing leukocytes.
  Article Google Scholar
• Gu, L., Tseng, S. C. & Rollins, B. J. Monocyte chemoattractant protein-1. Chem. Immunol. 72, 7–29 (1999).
  Article CAS PubMed Google Scholar
• Janatpour, M. J., Hudak, S., Sathe, M., Sedgwick, J. D. & McEvoy, L. M. Tumor necrosis factor-dependent segmental control of MIG expression by high endothelial venules in inflamed lymph nodes regulates monocyte recruitment. J. Exp. Med. 194, 1375–1384 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Nibbs, R. J. et al. The β-chemokine receptor D6 is expressed by lymphatic endothelium and a subset of vascular tumors. Am. J. Pathol. 158, 867–877 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Fra, A. M. et al. Cutting edge: scavenging of inflammatory CC chemokines by the promiscuous putatively silent chemokine receptor D6. J. Immunol. 170, 2279–2282 (2003).
  Article CAS PubMed Google Scholar
• Girard, J. P. et al. Heterogeneity of endothelial cells: the specialized phenotype of human high endothelial venules characterized by suppression subtractive hybridization. Am. J. Pathol. 155, 2043–2055 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• De Bruyn, P. P. H. & Cho, Y. in Reaction Patterns of the Lymph Node (eds Grundman, E. & Vollmer, T.) 85–103 (Springer–Verlag, Berlin, 1990).
  Book Google Scholar
• Anderson, A. O. & Anderson, N. D. Lymphocyte emigration from high endothelial venules in rat lymph nodes. Immunology 31, 731–748 (1976).
  CAS PubMed PubMed Central Google Scholar
• Banchereau, J. et al. Immunobiology of dendritic cells. Annu. Rev. Immunol. 18, 767–811 (2000).
  Article CAS PubMed Google Scholar
• Sallusto, F. & Lanzavecchia, A. Mobilizing dendritic cells for tolerance, priming, and chronic inflammation. J. Exp. Med. 189, 611–614 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Jung, S. et al. In vivo depletion of CD11c+ dendritic cells abrogates priming of CD8+ T cells by exogenous cell-associated antigens. Immunity 17, 211–220 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Itano, A. A. et al. Distinct dendritic cell populations sequentially present a subcutaneous antigen to CD4+ T cells and stimulate different aspects of cell-mediated immunity. Immunity 19, 47–57 (2003).
  Article CAS PubMed Google Scholar
• Henri, S. et al. The dendritic cell populations of mouse lymph nodes. J. Immunol. 167, 741–748 (2001).
  Article CAS PubMed Google Scholar
• Nakano, H., Yanagita, M. & Gunn, M. D. CD11c+B220+Gr-1+ cells in mouse lymph nodes and spleen display characteristics of plasmacytoid dendritic cells. J. Exp. Med. 194, 1171–1178 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Stoitzner, P. et al. Visualization and characterization of migratory Langerhans cells in murine skin and lymph nodes by antibodies against Langerin/CD207. J. Invest. Dermatol. 120, 266–274 (2003).
  Article CAS PubMed Google Scholar
• Merad, M., Fong, L., Bogenberger, J. & Engleman, E. G. Differentiation of myeloid dendritic cells into CD8α-positive dendritic cells in vivo. Blood 96, 1865–1872 (2000).
  Article CAS PubMed Google Scholar
• Cella, M. et al. Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nature Med. 5, 919–923 (1999).
  Article CAS PubMed Google Scholar
• Merad, M. et al. Langerhans cells renew in the skin throughout life under steady-state conditions. Nature Immunol. 3, 1135–1141 (2002).
  Article CAS Google Scholar
• Robert, C. et al. Interaction of dendritic cells with skin endothelium: a new perspective on immunosurveillance. J. Exp. Med. 189, 627–636 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Randolph, G. J., Inaba, K., Robbiani, D. F., Steinman, R. M. & Muller, W. A. Differentiation of phagocytic monocytes into lymph node dendritic cells in vivo. Immunity 11, 753–761 (1999).
  Article CAS PubMed Google Scholar
• Sallusto, F. et al. Rapid and coordinated switch in chemokine receptor expression during dendritic cell maturation. Eur. J. Immunol. 28, 2760–2769 (1998).
  Article CAS PubMed Google Scholar
• Adema, G. J. et al. A dendritic-cell-derived C-C chemokine that preferentially attracts naive T cells. Nature 387, 713–717 (1997).
  Article CAS PubMed Google Scholar
• Hieshima, K. et al. A novel human CC chemokine PARC that is most homologous to macrophage-inflammatory protein-1α/LD78α and chemotactic for T lymphocytes, but not for monocytes. J. Immunol. 159, 1140–1149 (1997).
  CAS PubMed Google Scholar
• Godiska, R. et al. Human macrophage-derived chemokine (MDC), a novel chemoattractant for monocytes, monocyte-derived dendritic cells, and natural killer cells J. Exp. Med. 185, 1595–1604 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Ngo, V. N., Tang, H. L. & Cyster, J. G. Epstein–Barr-virus-induced molecule 1 ligand chemokine is expressed by dendritic cells in lymphoid tissues and strongly attracts naive T cells and activated B cells. J. Exp. Med. 188, 181–191 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Kabashima, K. et al. Thromboxane A2 modulates interaction of dendritic cells and T cells and regulates acquired immunity. Nature Immunol. 4, 694–701 (2003).
  Article CAS Google Scholar
• Robbiani, D. F. et al. The leukotriene C(4) transporter MRP1 regulates CCL19 (MIP-3β, ELC)-dependent mobilization of dendritic cells to lymph nodes. Cell 103, 757–768 (2000).
  Article CAS PubMed Google Scholar
• Xu, H. et al. The role of ICAM-1 molecule in the migration of Langerhans cells in the skin and regional lymph node. Eur. J. Immunol. 31, 3085–3093 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Steinman, R. M. & Nussenzweig, M. C. Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc. Natl Acad. Sci. USA 99, 351–358 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Garside, P. et al. Visualization of specific B and T lymphocyte interactions in the lymph node. Science 281, 96–99 (1998). This study uses immunohistochemistry to characterize the kinetics and interstitial location of interactions between antigen-specific B and T cells in lymph nodes.
  Article CAS PubMed Google Scholar
• Denk, W., Strickler, J. H. & Webb, W. W. Two-photon laser scanning fluorescence microscopy. Science 248, 73–76 (1990).
  Article CAS PubMed Google Scholar
• Cahalan, M. D., Parker, I., Wei, S. H. & Miller, M. J. Two-photon tissue imaging: seeing the immune system in a fresh light. Nature Rev. Immunol. 2, 872–880 (2002).
  Article CAS Google Scholar
• Miller, M. J., Wei, S. H., Parker, I. & Cahalan, M. D. Two-photon imaging of lymphocyte motility and antigen response in intact lymph node. Science 296, 1869–1873 (2002). This study uses time-lapse two-photon microscopy to study the dynamics of T-cell migration in excised LNs.
  Article CAS PubMed Google Scholar
• Stoll, S., Delon, J., Brotz, T. M. & Germain, R. N. Dynamic imaging of T cell–dendritic cell interactions in lymph nodes. Science 296, 1873–1876 (2002).
  Article PubMed Google Scholar
• Bousso, P. & Robey, E. Dynamics of CD8+ T cell priming by dendritic cells in intact lymph nodes. Nature Immunol. 4, 579–585 (2003).
  Article CAS Google Scholar
• von Andrian, U. H. Immunology. T cell activation in six dimensions. Science 296, 1815–1817 (2002).
  Article CAS PubMed Google Scholar
• Torres Filho, I. P., Leunig, M., Yuan, F., Intaglietta, M. & Jain, R. K. Noninvasive measurement of microvascular and interstitial oxygen profiles in a human tumor in SCID mice. Proc. Natl Acad. Sci. USA 91, 2081–2085 (1994).
  Article CAS PubMed PubMed Central Google Scholar
• Bogdan, C., Rollinghoff, M. & Diefenbach, A. Reactive oxygen and reactive nitrogen intermediates in innate and specific immunity. Curr. Opin. Immunol. 12, 64–76 (2000).
  Article CAS PubMed Google Scholar
• Droge, W. Free radicals in the physiological control of cell function. Physiol. Rev. 82, 47–95 (2002).
  Article CAS PubMed Google Scholar
• Madden, K. S. & Felten, D. L. Experimental basis for neural-immune interactions. Physiol. Rev. 75, 77–106 (1995).
  Article CAS PubMed Google Scholar
• Miller, M. J., Wei, S. H., Cahalan, M. D. & Parker, I. Autonomous T cell trafficking examined in vivo with intravital two-photon microscopy. Proc. Natl Acad. Sci. USA 100, 2604–2609 (2003). This is the first two-photon microscopy study on T-cell migration in LNs in vivo . The data indicate that T cells migrate rapidly and without apparent directionality in the T-cell area immediately after having undergone diapedesis across the HEVs.
  Article CAS PubMed PubMed Central Google Scholar
• Legler, D. F. et al. B cell-attracting chemokine 1, a human CXC chemokine expressed in lymphoid tissues, selectively attracts B lymphocytes via BLR1/CXCR5. J. Exp. Med. 187, 655–660 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Forster, R. et al. A putative chemokine receptor, BLRI, directs B cell migration to defined lymphoid organs and specific anatomic compartments of the spleen. Cell 87, 1037–1047 (1996).
  Article CAS PubMed Google Scholar
• Schaerli, P. et al. CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J. Exp. Med. 192, 1553–1562 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Breitfeld, D. et al. Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J. Exp. Med. 192, 1545–1552 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Irjala, H. et al. The same endothelial receptor controls lymphocyte traffic both in vascular and lymphatic vessels. Eur. J. Immunol. 33, 815–824 (2003).
  Article CAS PubMed Google Scholar
• Napoli, K. L. The FTY720 story. Ther. Drug Monit. 22, 47–51 (2000).
  Article CAS PubMed Google Scholar
• Brinkmann, V. & Lynch, K. FTY720: targeting G-protein-coupled receptors for sphingosine-1-phosphate in transplantation and autoimmunity. Curr. Opin. Immunol. 14, 569–575 (2002).
  Article CAS PubMed Google Scholar
• Enosawa, S., Suzuki, S., Kakefuda, T., Li, X. K. & Amemiya, H. Induction of selective cell death targeting on mature T-lymphocytes in rats by a novel immunosuppressant, FTY720. Immunopharmacology 34, 171–179 (1996).
  Article CAS PubMed Google Scholar
• Pinschewer, D. D. et al. FTY720 immunosuppression impairs effector T cell peripheral homing without affecting induction, expansion, and memory. J. Immunol. 164, 5761–5770 (2000).
  Article CAS PubMed Google Scholar
• Chiba, K. et al. FTY720, a novel immunosuppressant, induces sequestration of circulating mature lymphocytes by acceleration of lymphocyte homing in rats. I. FTY720 selectively decreases the number of circulating mature lymphocytes by acceleration of lymphocyte homing. J. Immunol. 160, 5037–5044 (1998).
  CAS PubMed Google Scholar
• Henning, G. et al. CC chemokine receptor 7-dependent and -independent pathways for lymphocyte homing: modulation by FTY720. J. Exp. Med. 194, 1875–1881 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Yagi, H. et al. Immunosuppressant FTY720 inhibits thymocyte emigration. Eur. J. Immunol. 30, 1435–1444 (2000).
  Article CAS PubMed Google Scholar
• Mandala, S. et al. Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science 296, 346–349 (2002). This study shows that the immunosuppressive drug FTY720 is rapidly phosphorylated in vivo and then binds to sphingosine-1-phosphate (S1P) receptors. S1P-receptor agonists cause lymphopaenia and block lymphocyte exit from the LN parenchyma to the medullary sinuses.
  Article CAS PubMed Google Scholar
• Brinkmann, V. et al. The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J. Biol. Chem. 277, 21453–21457 (2002).
  Article CAS PubMed Google Scholar
• Graeler, M., Shankar, G. & Goetzl, E. J. Cutting edge: suppression of T cell chemotaxis by sphingosine 1-phosphate. J. Immunol. 169, 4084–4087 (2002).
  Article CAS PubMed Google Scholar
• Honig, S. M. et al. FTY720 stimulates multidrug transporter- and cysteinyl leukotriene-dependent T cell chemotaxis to lymph nodes. J. Clin. Invest. 111, 627–637 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• von Andrian, U. H., Hasslen, S. R., Nelson, R. D., Erlandsen, S. L. & Butcher, E. C. A central role for microvillous receptor presentation in leukocyte adhesion under flow. Cell 82, 989–999 (1995).
  Article CAS PubMed Google Scholar
• Zoumi, A., Yeh, A. & Tromberg, B. J. Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two–photon excited fluorescence. Proc. Natl Acad. Sci. USA 99, 11014–11019 (2002).
  Article CAS PubMed PubMed Central Google Scholar