Migration, Cell–Cell Interaction and Adhesion in the Immune System

Conference paper
Part of the Ernst Schering Foundation Symposium Proceedings book series (SCHERING FOUND, volume 2007/3)


Migration is an essential function of immune cells. It is necessary to lead immune cell precursors from their site of generation to the places of maturation or function. Cells of the adaptive immune system also need to interact physically with each other or with specialized antigen presenting cells in lymphatic tissues in order to become activated. Thereby a complex series of controlled migration events, adhesive interactions and signalling responses is induced. Finally cells must be able to leave the activating tissues and re-enter the bloodstream from which they extravasate into inflamed tissue sites. Cells of the innate immune system can function directly without the need for previous activation. However, these cells have to adapt their function to a panoply of pathogens and environmental niches which can be invaded. The current review highlights the central aspects of cellular dynamics underlying adaptive and innate cellular immunity. Thereby a focus will be put on recent results obtained by microscopic observation of live cells in vitro or by intravital 2-photon microscopy in live animals.


Dendritic Cell Antigen Present Cell Chronic Granulomatous Disease Follicular Dendritic Cell Mature Dendritic Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Ackerman AL, Cresswell P (2004) Cellular mechanisms governing cross-presentation of exogenous antigens. Nat Immunol 5:678–684PubMedCrossRefGoogle Scholar
  2. Adams GB, Chabner KT, Alley IR, Olson DP, Szczepiorkowski ZM, Poznansky MC, Kos CH, Pollak MR, Brown EM, Scadden DT (2006) Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor. Nature 439:599–603PubMedCrossRefGoogle Scholar
  3. Akira S, Takeda K (2004) Toll-like receptor signalling. Nat Rev Immunol 4:499–511PubMedCrossRefGoogle Scholar
  4. Allen CD, Okada T, Tang HL, Cyster JG (2007) Imaging of germinal center selection events during affinity maturation. Science 315:528–531PubMedCrossRefGoogle Scholar
  5. Aydar Y, Sukumar S, Szakal AK, Tew JG (2005) The influence of immune complex-bearing follicular dendritic cells on the IgM response, Ig class switching, and production of high affinity IgG. J Immunol 174:5358–5366PubMedGoogle Scholar
  6. Babbitt BP, Allen PM, Matsueda G, Haber E, Unanue ER (1985) Binding of immunogenic peptides to Ia histocompatibility molecules. Nature 317:359–361PubMedCrossRefGoogle Scholar
  7. Banchereau J, Bazan F, Blanchard D, Briere F, Galizzi JP, van Kooten C, Liu YJ, Rousset F, Saeland S (1994) The CD40 antigen and its ligand. Annu Rev Immunol 12:881–922PubMedCrossRefGoogle Scholar
  8. Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K (2000) Immunobiology of dendritic cells. Annu Rev Immunol 18:767–811PubMedCrossRefGoogle Scholar
  9. Banchereau J, Palucka AK (2005) Dendritic cells as therapeutic vaccines against cancer. Nat Rev Immunol 5:296–306PubMedCrossRefGoogle Scholar
  10. Behnsen J, Narang P, Hasenberg M, Gunzer F, Bilitewski U, Klippel N, Rohde M, Brock M, Brakhage AA, Gunzer M (2007) Environmental dimensionality controls the interaction of phagocytes with the pathogenic fungi Aspergillus fumigatus and Candida albicans. PLoS Pathog 3:e13PubMedCrossRefGoogle Scholar
  11. Benham A, Tulp A, Neefjes J (1995) Synthesis and assembly of MHC-peptide-complexes. Immunol Today 16:359–362PubMedCrossRefGoogle Scholar
  12. Berlin C, Bargatze RF, Campbell JJ, von Andrian UH, Szabo MC, Hasslen SR, Nelson RD, Berg EL, Erlandsen SL, Butcher EC (1995) α4 Integrins mediate lymphocyte attachment and rolling under physiologic flow. Cell 80:413–422PubMedCrossRefGoogle Scholar
  13. Bhakta NR, Oh DY, Lewis RS (2005) Calcium oscillations regulate thymocyte motility during positive selection in the three-dimensional thymic environment. Nat Immunol 6:143–151PubMedCrossRefGoogle Scholar
  14. Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC (1987a) Structure of the human class I histocompatibility antigen, HLA-A2. Nature 329:506–512PubMedCrossRefGoogle Scholar
  15. Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC (1987b) The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature 329:512–518PubMedCrossRefGoogle Scholar
  16. Boehm T, Bleul CC (2006) Thymus-homing precursors and the thymic microenvironment. Trends Immunol 27:477–484PubMedCrossRefGoogle Scholar
  17. Bonnett CR, Cornish EJ, Harmsen AG, Burritt JB (2006) Early neutrophil recruitment and aggregation in the murine lung inhibit germination of Aspergillus fumigatus conidia. Infect Immun 74:6528–6539PubMedCrossRefGoogle Scholar
  18. Bousso P, Bhakta NR, Lewis RS, Robey E (2002) Dynamics of thymocyte-stromal cell interactions visualized by two-photon microscopy. Science 296:1876–1880PubMedCrossRefGoogle Scholar
  19. Bousso P, Robey E (2003) Dynamics of CD8(+) T cell priming by dendritic cells in intact lymph nodes. Nat Immunol 4:579–585PubMedCrossRefGoogle Scholar
  20. Bousso P, Robey EA (2004) Dynamic behavior of T cells and thymocytes in lymphoid organs as revealed by two-photon microscopy. Immunity 21:349–355PubMedCrossRefGoogle Scholar
  21. Boyden S (1962) The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leucocytes. J Exp Med 115:453–466PubMedCrossRefGoogle Scholar
  22. Breitfeld D, Ohl L, Kremmer E, Ellwart J, Sallusto F, Lipp M, Forster R (2000) Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J Exp Med 192:1545–1552PubMedCrossRefGoogle Scholar
  23. Brossard C, Feuillet V, Schmitt A, Randriamampita C, Romao M, Raposo G, Trautmann A (2005) Multifocal structure of the T cell—dendritic cell synapse. Eur J Immunol 35:1741–1753PubMedCrossRefGoogle Scholar
  24. Cahalan MD, Parker I, Wei SH, Miller MJ (2002) Two-photon tissue imaging: seeing the immune system in a fresh light. Nat Rev Immunol 2:872–880PubMedCrossRefGoogle Scholar
  25. Campi G, Varma R, Dustin ML (2005) Actin and agonist MHC-peptide complex-dependent T cell receptor microclusters as scaffolds for signaling. J Exp Med 202:1031–1036PubMedCrossRefGoogle Scholar
  26. Castellino F, Huang AY, tan-Bonnet G, Stoll S, Scheinecker C, Germain RN (2006) Chemokines enhance immunity by guiding naive CD8+ T cells to sites of CD4+ T cell-dendritic cell interaction. Nature 440:890–895PubMedCrossRefGoogle Scholar
  27. Chiba K, Yanagawa Y, Masubuchi Y, Kataoka H, Kawaguchi T, Ohtsuki M, Hoshino Y (1998) 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 160:5037–5044PubMedGoogle Scholar
  28. Chow AY, Mellman I (2005) Old lysosomes, new tricks: MHC II dynamics in DCs. Trends Immunol 26:72–78PubMedCrossRefGoogle Scholar
  29. Christopher MJ, Link DC (2007) Regulation of neutrophil homeostasis. Curr Opin Hematol 14:3–8PubMedCrossRefGoogle Scholar
  30. Crawford A, Macleod M, Schumacher T, Corlett L, Gray D (2006) Primary T cell expansion and differentiation in vivo requires antigen presentation by B cells. J Immunol 176:3498–3506PubMedGoogle Scholar
  31. Cyster JG (1999) Chemokines and cell migration in secondary lymphoid organs. Science 286:2098–2102PubMedCrossRefGoogle Scholar
  32. de Vinuesa CG, Cook MC, Ball J, Drew M, Sunners Y, Cascalho M, Wabl M, Klaus GG, MacLennan IC (2000) Germinal centers without T cells. J Exp Med 191:485–494PubMedCrossRefGoogle Scholar
  33. Diebold SS, Kaisho T, Hemmi H, Akira S, Reis e Sousa C (2004) Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303:1529–1531PubMedCrossRefGoogle Scholar
  34. Donnadieu E, Revy P, Trautmann A (2001) Imaging T-cell antigen recognition and comparing immunological and neuronal synapses. Immunology 103:417–425PubMedCrossRefGoogle Scholar
  35. Dorner B, Müller S, Entschladen F, Schröder JM, Franke P, Kraft R, Friedl P, Clark-Lewis I, Kroczek RA (1997) Purification, structural analysis, and function of ATAC, a cytokine secreted by CD8+ T cells. J Biol Chem 272:8817–8823PubMedCrossRefGoogle Scholar
  36. Dustin ML (2004) New ways for lyphocytes to meet. Blood 104:2618–2619CrossRefGoogle Scholar
  37. Dustin ML (2005) A dynamic view of the immunological synapse. Semin Immunol 17:400–410PubMedCrossRefGoogle Scholar
  38. Dustin ML, Allen PM, Shaw AS (2001) Environmental control of immunological synapse formation and duration. Trends Immunol 22:192–194PubMedCrossRefGoogle Scholar
  39. Dustin ML, Chan AC (2000) Signaling takes shape in the immune system. Cell 103:283–294PubMedCrossRefGoogle Scholar
  40. Dustin ML, de Fougerolles AR (2001) Reprograming T cells: the role of extracellular matrix in coordination of T cell activation and migration. Curr Opin Immunol 13:286–290PubMedCrossRefGoogle Scholar
  41. Ebnet K, Vestweber D (1999) Molecular mechanisms that control leukocyte extravasation: the selectins and the chemokines. Histochem Cell Biol 112:1–23PubMedCrossRefGoogle Scholar
  42. Entschladen F, Gunzer M, Scheuffele CM, Niggemann B, Zänker KS (2000) T lymphocytes and neutrophil granulocytes differ in regulatory signaling and migratory dynamics with regard to spontaneous locomotion and chemotaxis. Cell Immunol 199:104–114PubMedCrossRefGoogle Scholar
  43. Entschladen F, Niggemann B, Zänker KS, Friedl P (1997) Differential requirement of protein tyrosine kinases and protein kinase C in the regulation of T cell locomotion in three-dimensional collagen matrices. J Immunol 159:3203–3210PubMedGoogle Scholar
  44. Epstein MM, Di RF, Jankovic D, Sher A, Matzinger P (1995) Successful T cell priming in B cell-deficient mice. J Exp Med 182:915–922PubMedCrossRefGoogle Scholar
  45. Fillatreau S, Sweenie CH, McGeachy MJ, Gray D, Anderton SM (2002) B cells regulate autoimmunity by provision of IL-10. Nat Immunol 3:944–950PubMedCrossRefGoogle Scholar
  46. Förster R, Mattis AE, Kremmer E, Wolf E, Brem G, Lipp M (1996) A putative chemokine receptor, BLR1, directs B cell migration to defined lymphoid organs and specific anatomic compartments of the spleen. Cell 87:1037–1047PubMedCrossRefGoogle Scholar
  47. Förster R, Schubel A, Breitfeld D, Kremmer E, Renner-Müller I, Wolf E, Lipp M (1999) CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell 99:23–33PubMedCrossRefGoogle Scholar
  48. Friedl P, Entschladen F, Conrad C, Niggemann B, Zänker KS (1998) CD4+ T lymphocytes migrating in three-dimensional collagen lattices lack focal adhesions and utilize beta1 integrin-independent strategies for polarization, interaction with collagen fibers and locomotion. Eur J Immunol 28:2331–2343PubMedCrossRefGoogle Scholar
  49. Friedl P, Gunzer M (2001) Interaction of T cells with APCs: the serial encounter model. Trends Immunol 22:187–191PubMedCrossRefGoogle Scholar
  50. Friedl P, Noble PB, Shields ED, Zänker KS (1994) Locomotor phenotypes of unstimulated CD45RAhigh and CD45ROhigh CD4+ and CD8+ lymphocytes in three-dimensional collagen lattices. Immunology 82:617–624PubMedGoogle Scholar
  51. Friedl P, Noble PB, Zänker KS (1993) Lymphocyte migration in three-dimensional collagen gels. Comparison of three quantitative methods for analysing cell trajectories. J Immunol Meth 165:157–165CrossRefGoogle Scholar
  52. Friedl P, Noble PB, Zänker KS (1995) T Lymphocyte locomotion in a three-dimensional collagen matrix. Expression and function of cell adhesion molecules. J Immunol 154:4973–4985PubMedGoogle Scholar
  53. Fuchs EJ, Matzinger P (1992) B cells turn off virgin but not memory T cells. Science 258:1156–1159PubMedCrossRefGoogle Scholar
  54. Galkina E, Tanousis K, Preece G, Tolaini M, Kioussis D, Florey O, Haskard DO, Tedder TF, Ager A (2003) L-selectin shedding does not regulate constitutive T cell trafficking but controls the migration pathways of antigen-activated T lymphocytes. J Exp Med 198:1323–1335PubMedCrossRefGoogle Scholar
  55. Garcia Z, Pradelli E, Celli S, Beuneu H, Simon A, Bousso P (2007) Competition for antigen determines the stability of T cell-dendritic cell interactions during clonal expansion. Proc Natl Acad Sci USA 104:4553–4558PubMedCrossRefGoogle Scholar
  56. Garlanda C, Hirsch E, Bozza S, Salustri A, De Acetis M, Nota R, Maccagno A, Riva F, Bottazzi B, Peri G, Doni A, Vago L, Botto M, De Santis R, Carminati P, Siracusa G, Altruda F, Vecchi A, Romani L, Mantovani A (2002) Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response. Nature 420:182–186PubMedCrossRefGoogle Scholar
  57. Garside P, Ingulli E, Merica RR, Johnson JG, Noelle RJ, Jenkins MK (1998) Visualization of specific B and T lymphocyte interactions in the lymph node. Science 281:96–99PubMedCrossRefGoogle Scholar
  58. Gehr P, Green FH, Geiser M, Im HV, Lee MM, Schurch S (1996) Airway surfactant, a primary defense barrier: mechanical and immunological aspects. J Aerosol Med 9:163–181PubMedCrossRefGoogle Scholar
  59. Geiser M (2002) Morphological aspects of particle uptake by lung phagocytes. Microsc Res Tech 57:512–522PubMedCrossRefGoogle Scholar
  60. Geiser M, Bastian S (2003) Surface-lining layer of airways in cystic fibrosis mice. Am J Physiol Lung Cell Mol Physiol 285:L1277–L1285PubMedGoogle Scholar
  61. Germain RN (2002) T-cell development and the CD4-CD8 lineage decision. Nat Rev Immunol 2:309–322PubMedCrossRefGoogle Scholar
  62. Germain RN, Jenkins MK (2004) In vivo antigen presentation. Curr Opin Immunol 16:120–125PubMedCrossRefGoogle Scholar
  63. Godin I, Cumano A (2005) Of birds and mice: hematopoietic stem cell development. Int J Dev Biol 49:251–257PubMedCrossRefGoogle Scholar
  64. Grakoui A, Bromley SK, Sumen C, Davis MM, Shaw AS, Allen PM, Dustin ML (1999) The immunological synapse: a molecular machine controlling T cell activation. Science 285:221–227PubMedCrossRefGoogle Scholar
  65. Gunzer M, Friedl P, Niggemann B, Bröcker E-B, Kämpgen E, Zänker KS (2000a) Migration of dendritic cells within 3-D collagen lattices is dependent on tissue origin, state of maturation, and matrix structure and is maintained by proinflammatory cytokines. J Leukoc Biol 67:622–629PubMedGoogle Scholar
  66. Gunzer M, Janich S, Varga G, Grabbe S (2001) Dendritic cells and tumor immunity. Semin Immunol 13:291–302PubMedCrossRefGoogle Scholar
  67. Gunzer M, Kämpgen E, Bröcker E-B, Zänker KS, Friedl P (1997) Migration of dendritic cells in 3D-collagen lattices: visualisation of dynamic interactions with the substratum and the distribution of surface structures via a novel confocal reflection imaging technique. Adv Exp Med Biol 417:97–103PubMedGoogle Scholar
  68. Gunzer M, Riemann H, Basoglu Y, Hillmer A, Weishaupt C, Balkow S, Benninghoff B, Ernst B, Steinert M, Scholzen T, Sunderkotter C, Grabbe S (2005) Systemic administration of a TLR7 ligand leads to transient immune incompetence due to peripheral blood leukocyte depletion. Blood 106:2424–2432PubMedCrossRefGoogle Scholar
  69. Gunzer M, Schäfer A, Borgmann S, Grabbe S, Zänker KS, Bröcker E-B, Kämpgen E, Friedl P (2000b) Antigen presentation in extracellular matrix: interactions of T cells with dendritic cells are dynamic, short lived, and sequential. Immunity 13:323–332PubMedCrossRefGoogle Scholar
  70. Gunzer M, Weishaupt C, Hillmer A, Basoglu Y, Friedl P, Dittmar KE, Kolanus W, Varga G, Grabbe S (2004) A spectrum of biophysical interaction modes between T cells and different antigen presenting cells during priming in 3-D collagen and in vivo. Blood 104:2801–2809PubMedCrossRefGoogle Scholar
  71. Hardtke S, Ohl L, Forster R (2005) Balanced expression of CXCR5 and CCR7 on follicular T helper cells determines their transient positioning to lymph node follicles and is essential for efficient B-cell help. Blood 106:1924–1931PubMedCrossRefGoogle Scholar
  72. Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT (2005) Interleukin 17-producing CD4(+) effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6:1123–1132PubMedCrossRefGoogle Scholar
  73. Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, Lipford G, Wagner H, Bauer S (2004) Species-specific recognition of single-stranded RNA via Toll-like receptor 7 and 8. Science 303:1526–1529PubMedCrossRefGoogle Scholar
  74. Huang NN, Han SB, Hwang IY, Kehrl JH (2005) B cells productively engage soluble antigen-pulsed dendritic cells: visualization of live-cell dynamics of B cell-dendritic cell interactions. J Immunol 175:7125–7134PubMedGoogle Scholar
  75. Hugues S, Fetler L, Bonifaz L, Helft J, Amblard F, Amigorena S (2004) Distinct T cell dynamics in lymph nodes during the induction of tolerance and immunity. Nat Immunol 5:1235–1242PubMedCrossRefGoogle Scholar
  76. Hwang JM, Yamanouchi J, Santamaria P, Kubes P (2004) A critical temporal window for selectin-dependent CD4+ lymphocyte homing and initiation of late-phase inflammation in contact sensitivity. J Exp Med 199:1223–1234PubMedCrossRefGoogle Scholar
  77. Iezzi G, Karjalainen K, Lanzavecchia A (1998) The duration of antigenic stimulation determines the fate of naive and effector T cells. Immunity 8:89–95PubMedCrossRefGoogle Scholar
  78. Kaufmann SH, McMichael AJ (2005) Annulling a dangerous liaison: vaccination strategies against AIDS and tuberculosis. Nat Med 11:S33–S44PubMedCrossRefGoogle Scholar
  79. Knoechel B, Lohr J, Kahn E, Abbas AK (2005) Cutting edge: the link between lymphocyte deficiency and autoimmunity: roles of endogenous T and B lymphocytes in tolerance. J Immunol 175:21–26PubMedGoogle Scholar
  80. Kosco-Vilbois MH (2003) Opinion: are follicular dendritic cells really good for nothing? Nat Rev Immunol 3:764–769PubMedCrossRefGoogle Scholar
  81. Lanzavecchia A, Iezzi G, Viola A (1999) From TCR engagement to T cell activation: a kinetic view of T cell behavior. Cell 96:1–4PubMedCrossRefGoogle Scholar
  82. Lanzavecchia A, Sallusto F (2001a) Antigen decoding by T lymphocytes: from synapses to fate determination. Nat Immunol 2:487–492PubMedCrossRefGoogle Scholar
  83. Lanzavecchia A, Sallusto F (2001b) The instructive role of dendritic cells on T cell responses: lineages, plasticity and kinetics. Curr Opin Immunol 13:291–298PubMedCrossRefGoogle Scholar
  84. Lassila O, Vainio O, Matzinger P (1988) Can B cells turn on virgin T cells? Nature 334:253–255PubMedCrossRefGoogle Scholar
  85. Latge JP (1999) Aspergillus fumigatus and aspergillosis. Clin Microbiol Rev 12:310–350PubMedGoogle Scholar
  86. Latge JP (2001) The pathobiology of Aspergillus fumigatus. Trends Microbiol 9:382–389PubMedCrossRefGoogle Scholar
  87. Lee KH, Dinner AR, Tu C, Campi G, Raychaudhuri S, Varma R, Sims TN, Burack WR, Wu H, Wang J, Kanagawa O, Markiewicz M, Allen PM, Dustin ML, Chakraborty AK, Shaw AS (2003) The immunological synapse balances T cell receptor signaling and degradation. Science 302:1218–1222PubMedCrossRefGoogle Scholar
  88. Lee KH, Holdorf AD, Dustin ML, Chan AC, Allen PM, Shaw AS (2002) T cell receptor signaling precedes immunological synapse formation. Science 295:1539–1542PubMedCrossRefGoogle Scholar
  89. Lindquist RL, Shakhar G, Dudziak D, Wardemann H, Eisenreich T, Dustin ML, Nussenzweig MC (2004) Visualizing dendritic cell networks in vivo. Nat Immunol 5:1243–1250PubMedCrossRefGoogle Scholar
  90. Lipsky PE, Rosenthal AS (1975) Macrophage-lymphocyte interaction. II. Antigen-mediated physical interactions between immune guinea pig lymph node lymphocytes and syngeneic macrophages. J Exp Med 141:138–154PubMedCrossRefGoogle Scholar
  91. Lo CG, Xu Y, Proia RL, Cyster JG (2005) Cyclical modulation of sphingosine-1-phosphate receptor 1 surface expression during lymphocyte recirculation and relationship to lymphoid organ transit. J Exp Med 201:291–301PubMedCrossRefGoogle Scholar
  92. MacLennan IC (1994) Germinal centers. Annu Rev Immunol 12:117–139PubMedCrossRefGoogle Scholar
  93. Maldonado RA, Irvine DJ, Schreiber R, Glimcher LH (2004) A role for the immunological synapse in lineage commitment of CD4 lymphocytes. Nature 431:527–532PubMedCrossRefGoogle Scholar
  94. Manitz MP, Horst B, Seeliger S, Strey A, Skryabin BV, Gunzer M, Frings W, Schonlau F, Roth J, Sorg C, Nacken W (2003) Loss of S100A9 (MRP14) results in reduced interleukin-8-induced CD11b surface expression, a polarized microfilament system, and diminished responsiveness to chemoattractants in vitro. Mol Cell Biol 23:1034–1043PubMedCrossRefGoogle Scholar
  95. Manser T (2004) Textbook germinal centers? J Immunol 172:3369–3375PubMedGoogle Scholar
  96. Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M (2004) The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 25:677–686PubMedCrossRefGoogle Scholar
  97. Matloubian M, Lo CG, Cinamon G, Lesneski MJ, Xu Y, Brinkmann V, Allende ML, Proia RL, Cyster JG (2004) Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 427:355–360PubMedCrossRefGoogle Scholar
  98. Matthias P, Rolink AG (2005) Transcriptional networks in developing and mature B cells. Nat Rev Immunol 5:497–508PubMedCrossRefGoogle Scholar
  99. Matzinger P (1994) Tolerance, danger, and the extended family. Annu Rev Immunol 12:991–1045PubMedCrossRefGoogle Scholar
  100. Mempel TR, Henrickson SE, von Andrian UH (2004) T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature 427:154–159PubMedCrossRefGoogle Scholar
  101. Mempel TR, Pittet MJ, Khazaie K, Weninger W, Weissleder R, von Boehmer H, von Andrian UH (2006) Regulatory T cells reversibly suppress cytotoxic T cell function independent of effector differentiation. Immunity 25:129–141PubMedCrossRefGoogle Scholar
  102. Metchnikoff II (1883) Untersuchungen über die Mesodermalen Phagozyten einiger Wirbeltiere. Biol Zent Bl 3:560–565Google Scholar
  103. Meyer-Hermann ME, Maini PK (2005) Cutting edge: back to `one-way' germinal centers. J Immunol 174:2489–2493PubMedGoogle Scholar
  104. Miller MJ, Hejazi AS, Wei SH, Cahalan MD, Parker I (2004a) T cell repertoire scanning is promoted by dynamic dendritic cell behavior and random T cell motility in the lymph node. Proc Natl Acad Sci USA 101:998–1003PubMedCrossRefGoogle Scholar
  105. Miller MJ, Safrina O, Parker I, Cahalan MD (2004b) Imaging the Single Cell Dynamics of CD4+ T Cell Activation by Dendritic Cells in Lymph Nodes. J Exp Med 200:847–856PubMedCrossRefGoogle Scholar
  106. Miller MJ, Wei SH, Parker I, Cahalan MD (2002) Two-photon imaging of lymphocyte motility and antigen response in intact lymph node. Science 296:1869–1873PubMedCrossRefGoogle Scholar
  107. Misslitz A, Pabst O, Hintzen G, Ohl L, Kremmer E, Petrie HT, Forster R (2004) Thymic T Cell Development and Progenitor Localization Depend on CCR7. J Exp Med 200:481–491PubMedCrossRefGoogle Scholar
  108. Mizoguchi A, Bhan AK (2006) A case for regulatory B cells. J Immunol 176:705–710PubMedGoogle Scholar
  109. Moghe PV, Nelson RD, Tranquillo RT (1995) Cytokine-stimulated chemotaxis of human neutrophils in a 3-D conjoined fibrin gel assay. J Immunol Methods 180:193–211PubMedCrossRefGoogle Scholar
  110. Monks CR, Freiberg BA, Kupfer H, Sciaky N, Kupfer A (1998) Three-dimensional segregation of supramolecular activation clusters in T cells. Nature 395:82–86PubMedCrossRefGoogle Scholar
  111. Moser K, Tokoyoda K, Radbruch A, MacLennan I, Manz RA (2006) Stromal niches, plasma cell differentiation and survival. Curr Opin Immunol 18:265–270PubMedCrossRefGoogle Scholar
  112. Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL (1986) Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136:2348–2357PubMedGoogle Scholar
  113. Mossman KD, Campi G, Groves JT, Dustin ML (2005) Altered TCR signaling from geometrically repatterned immunological synapses. Science 310:1191–1193PubMedCrossRefGoogle Scholar
  114. Murphy KM, Heimberger AB, Loh DY (1990) Induction by antigen of intrathymic apoptosis of CD4+CD8+TCRlo thymocytes in vivo. Science 250:1720–1723PubMedCrossRefGoogle Scholar
  115. Nathan C (2006) Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol 6:173–182PubMedCrossRefGoogle Scholar
  116. Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, Burg G, Schadendorf D (1998) Vaccination of melanoma patients with peptide -- or tumor lysate -- pulsed dendritic cells [see comments]. Nat Med 4:328–332PubMedCrossRefGoogle Scholar
  117. Newman SL, Bhugra B, Holly A, Morris RE (2005) Enhanced killing of Candida albicans by human macrophages adherent to type 1 collagen matrices via induction of phagolysosomal fusion. Infect Immun 73:770–777PubMedCrossRefGoogle Scholar
  118. Norbury CC, Basta S, Donohue KB, Tscharke DC, Princiotta MF, Berglund P, Gibbs J, Bennink JR, Yewdell JW (2004) CD8+ T cell cross-priming via transfer of proteasome substrates. Science 304:1318–1321PubMedCrossRefGoogle Scholar
  119. Okada T, Cyster JG (2006) B cell migration and interactions in the early phase of antibody responses. Curr Opin Immunol 18:278–285PubMedCrossRefGoogle Scholar
  120. Okada T, Miller MJ, Parker I, Krummel MF, Neighbors M, Hartley SB, O'Garra A, Cahalan MD, Cyster JG (2005) Antigen-engaged B cells undergo chemotaxis toward the T zone and form motile conjugates with helper T cells. PLoS Biol 3:e150PubMedCrossRefGoogle Scholar
  121. Okamoto S, Kawabata S, Nakagawa I, Okuno Y, Goto T, Sano K, Hamada S (2003) Influenza A virus-infected hosts boost an invasive type of Streptococcus pyogenes infection in mice. J Virol 77:4104–4112PubMedCrossRefGoogle Scholar
  122. Pabst R, Trepel F (1975) Quantitative evaluation of the total number and distribution of lymphocytes in young pigs. Blut 31:77–86PubMedCrossRefGoogle Scholar
  123. Peltola VT, McCullers JA (2004) Respiratory viruses predisposing to bacterial infections: role of neuraminidase. Pediatr Infect Dis J 23:S87–S97PubMedCrossRefGoogle Scholar
  124. Qi H, Egen JG, Huang AY, Germain RN (2006) Extrafollicular activation of lymph node B cells by antigen-bearing dendritic cells. Science 312:1672–1676PubMedCrossRefGoogle Scholar
  125. Quesniaux V, Fullard L, Arendse H, Davison G, Markgraaff N, Auer R, Ehrhart F, Kraus G, Schuurman HJ (1999) A novel immunosuppressant, FTY720, induces peripheral lymphodepletion of both T- and B cells and immunosuppression in baboons. Transpl Immunol 7:149–157PubMedCrossRefGoogle Scholar
  126. Reichardt P, Dornbach B, Song R, Beissert S, Gueler F, Loser K, Gunzer M (2007a) Naive B cells generate regulatory T cells in the presence of a mature immunological synapse. Blood (in press)Google Scholar
  127. Reichardt P, Gunzer F, Gunzer M (2007b) Analyzing the physicodynamics of immune cells in a 3-D collagen matrix. Methods Mol Biol (in press)Google Scholar
  128. Reichardt P, Gunzer M (2006) The biophysics of T lymphocyte activation in vitro and in vivo. In Cell Cell Communication in the Nervous and Immune System, B Schraven, E Gundelfinger, C Seidenbecher, eds. (Berlin, Heidelberg, New York: Springer-Verlag Berlin), pp 199–218Google Scholar
  129. Reif K, Ekland EH, Ohl L, Nakano H, Lipp M, Förster R, Cyster JG (2002) Balanced responsiveness to chemoattractants from adjacent zones determines B cell position. Nature 416:94–99PubMedCrossRefGoogle Scholar
  130. Reinhardt RL, Khoruts A, Merica R, Zell T, Jenkins MK (2001) Visualizing the generation of memory CD4 T cells in the whole body. Nature 410:101–105PubMedCrossRefGoogle Scholar
  131. Reis e Sousa C (2006) Dendritic cells in a mature age. Nat Rev Immunol 6:476–483PubMedCrossRefGoogle Scholar
  132. Richter A, Lohning M, Radbruch A (1999) Instruction for cytokine expression in T helper lymphocytes in relation to proliferation and cell cycle progression. J Exp Med 190:1439–1450PubMedCrossRefGoogle Scholar
  133. Rodriguez-Pinto D, Moreno J (2005) B cells can prime naive CD4(+) T cells in vivo in the absence of other professional antigen-presenting cells in a CD154-CD40-dependent manner. Eur J Immunol 35:1097–1105PubMedCrossRefGoogle Scholar
  134. Schiller M, Metze D, Luger TA, Grabbe S, Gunzer M (2006) Immune response modifiers—mode of action. Exp Dermatol 15:331–341PubMedCrossRefGoogle Scholar
  135. Schwab SR, Pereira JP, Matloubian M, Xu Y, Huang Y, Cyster JG (2005) Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients. Science 309:1735–1739PubMedCrossRefGoogle Scholar
  136. Schwickert TA, Lindquist RL, Shakhar G, Livshits G, Skokos D, Kosco-Vilbois MH, Dustin ML, Nussenzweig MC (2007) In vivo imaging of germinal centres reveals a dynamic open structure. Nature 446:83–87PubMedCrossRefGoogle Scholar
  137. Segal AW (2005) How neutrophils kill microbes. Annu Rev Immunol 23:197–223PubMedCrossRefGoogle Scholar
  138. Shiow LR, Rosen DB, Brdickova N, Xu Y, An J, Lanier LL, Cyster JG, Matloubian M (2006) CD69 acts downstream of interferon-alpha/beta to inhibit S1P(1) and lymphocyte egress from lymphoid organs. Nature 440:540–544PubMedCrossRefGoogle Scholar
  139. Shpacovitch VM, Varga G, Strey A, Gunzer M, Mooren F, Buddenkotte J, Vergnolle N, Sommerhoff CP, Grabbe S, Gerke V, Homey B, Hollenberg M, Luger TA, Steinhoff M (2004) Agonists of proteinase-activated receptor-2 modulate human neutrophil cytokine secretion, expression of cell adhesion molecules, and migration within 3-D collagen lattices. J Leukoc Biol 76:1–11CrossRefGoogle Scholar
  140. Snyderman R, Pike MC (1984) Chemoattractant receptors on phagocytic cells. Annu Rev Immunol 2:257–281PubMedCrossRefGoogle Scholar
  141. Sozzani S, Sallusto F, Luini W, Zhou D, Piemonti L, Allavena P, van Damme J, Valitutti S, Lanzavecchia A, Mantovani A (1995) Migration of dendritic cells in response to formyl peptides, C5a, and a distinct set of chemokines. J Immunol 155:3292–3295PubMedGoogle Scholar
  142. Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76:301–314PubMedCrossRefGoogle Scholar
  143. Steinman RM (1991) The dendritic cell system and its role in immunogenicity. Annu Rev Immunol 9:271–296PubMedCrossRefGoogle Scholar
  144. Steinman RM, Gutchinov B, Witmer MD, Nussenzweig MC (1983) Dendritic cells are the principal stimulators of the primary mixed leukocyte reaction in mice. J Exp Med 157:613PubMedCrossRefGoogle Scholar
  145. Steinman RM, Witmer MD (1978) Lymphoid dendritic cells are potent stimulators of the primary mixed leukocyte reaction in mice. Proc Natl Acad Sci USA 75:5132–5136PubMedCrossRefGoogle Scholar
  146. Stoll S, Delon J, Brotz TM, Germain RN (2002) Dynamic imaging of T cell-dendritic cell interactions in lymph nodes. Science 296:1873–1876PubMedCrossRefGoogle Scholar
  147. Suzuki N, Ohneda O, Minegishi N, Nishikawa M, Ohta T, Takahashi S, Engel JD, Yamamoto M (2006) Combinatorial Gata2 and Sca1 expression defines hematopoietic stem cells in the bone marrow niche. Proc Natl Acad Sci USA 103:2202–2207PubMedCrossRefGoogle Scholar
  148. Tadokoro CE, Shakhar G, Shen S, Ding Y, Lino AC, Maraver A, Lafaille JJ, Dustin ML (2006) Regulatory T cells inhibit stable contacts between CD4+ T cells and dendritic cells in vivo. J Exp Med 203:505–511PubMedCrossRefGoogle Scholar
  149. Takeda K, Kaisho T, Akira S (2003) Toll-Like Receptors. Annu Rev Immunol 21:335–376PubMedCrossRefGoogle Scholar
  150. Tang Q, Adams JY, Tooley AJ, Bi M, Fife BT, Serra P, Santamaria P, Locksley RM, Krummel MF, Bluestone JA (2006) Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic mice. Nat Immunol 7:83–92PubMedCrossRefGoogle Scholar
  151. Tarlinton D (1998) Germinal centers: form and function. Curr Opin Immunol 10:245–251PubMedCrossRefGoogle Scholar
  152. Tauber AI (2003) Metchnikoff and the phagocytosis theory. Nat Rev Mol Cell Biol 4:897–901PubMedCrossRefGoogle Scholar
  153. ThurnerB, Haendle I, Röder C, Dieckmann D, Keikavoussi P, Jonuleit H, Bender A, Maczek C, Schreiner D, von Den Driesch P, Bröcker E-B, Steinman RM, Enk A, Kämpgen E, Schuler G (1999) Vaccination with Mage-3A1 peptide-pulsed mature, monocyte-derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage IV melanoma. J Exp Med 190:1669–1678PubMedCrossRefGoogle Scholar
  154. Tortora GJ, Grabowski SR (2000). The respiratory system. In Principles of anatomy and physiology, GJ Tortora, SR Grabowski, eds. (New York; Chichester; Weinheim; Brisbane; Singapore; Toronto: John Wiley & Sons, Inc.), pp 775–817Google Scholar
  155. Trombetta ES, Mellman I (2005) Cell biology of antigen processing in vitro and in vivo. Annu Rev Immunol 23:975–1028PubMedCrossRefGoogle Scholar
  156. Tumpey TM, Lu X, Morken T, Zaki SR, Katz JM (2000) Depletion of lymphocytes and diminished cytokine production in mice infected with a highly virulent influenza A (H5N1) virus isolated from humans. J Virol 74:6105–6116PubMedCrossRefGoogle Scholar
  157. Underhill DM, Bassetti M, Rudensky A, Aderem A (1999) Dynamic interactions of macrophages with T cells during antigen presentation. J Exp Med 190:1909–1914PubMedCrossRefGoogle Scholar
  158. van der Merwe A, Davis SJ, Shaw AS, Dustin ML (2000) Cytoskeletal polarization and redistribution of cell-surface molecules during T cell antigen recognition. Semin Immunol 12:5–21CrossRefGoogle Scholar
  159. Verploegen S, Ulfman L, van Deutekom H, van Aalst C, Honing H, Lammers JW, Koenderman L, Coffer PJ (2005) Characterization of the role of CamKI Like Kinase (CKLiK) in human granulocyte function. Blood 106:1076–1083PubMedCrossRefGoogle Scholar
  160. von Andrian UH, M'Rini C (1998) In situ analysis of lymphocyte migration to lymph nodes. Cell Adhes Commun 6:85–96CrossRefGoogle Scholar
  161. von Andrian UH, Mempel TR (2003) Homing and cellular traffic in lymph nodes. Nat Rev Immunol 3:867–878CrossRefGoogle Scholar
  162. von Boehmer H, Aifantis I, Gounari F, Azogui O, Haughn L, Apostolou I, Jaeckel E, Grassi F, Klein L (2003) Thymic selection revisited: how essential is it? Immunol Rev 191:62–78CrossRefGoogle Scholar
  163. Warnock RA, Askari S, Butcher EC, von Andrian UH (1998) Molecular mechanisms of lymphocyte homing to peripheral lymph nodes. J Exp Med 187:205–216PubMedCrossRefGoogle Scholar
  164. Weninger W, Crowley MA, Manjunath N, von Andrian UH (2001) Migratory Properties of Naive, Effector, and Memory CD8+ T Cells. J Exp Med 194:953–966PubMedCrossRefGoogle Scholar
  165. Wilson A, Trumpp A (2006) Bone-marrow haematopoietic stem-cell niches. Nat Rev Immunol 6:93–106PubMedCrossRefGoogle Scholar
  166. Witt C, Raychaudhuri S, Chakraborty AK (2005a) Movies, measurement, and modeling: the three Ms of mechanistic immunology. J Exp Med 201:501–504PubMedCrossRefGoogle Scholar
  167. Witt CM, Raychaudhuri S, Schaefer B, Chakraborty AK, Robey EA (2005b) Directed migration of positively selected thymocytes visualized in real time. PLoS Biol 3:e160PubMedCrossRefGoogle Scholar
  168. Wolkers MC, Brouwenstijn N, Bakker AH, Toebes M, Schumacher TN (2004) Antigen bias in T cell cross-priming. Science 304:1314–1317PubMedCrossRefGoogle Scholar
  169. Yokosuka T, Sakata-Sogawa K, Kobayashi W, Hiroshima M, Hashimoto-Tane A, Tokunaga M, Dustin ML, Saito T (2005) Newly generated T cell receptor microclusters initiate and sustain T cell activation by recruitment of Zap70 and SLP-76. Nat Immunol 6:1253–1262PubMedCrossRefGoogle Scholar
  170. Zinkernagel RM (1996) Immunology taught by viruses. Science 271:173–178PubMedCrossRefGoogle Scholar
  171. Zinkernagel RM, Doherty PC (1974) Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature 248:701–702PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Institute of ImmunologyOtto-von-Gericke University MagdeburgMagdeburgGermany

Personalised recommendations