Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 7 June 2002:
Vol. 296. no. 5574, pp. 1873 - 1876
DOI: 10.1126/science.1071065
Prev | Table of Contents | Next

Reports

Dynamic Imaging of T Cell-Dendritic Cell Interactions in Lymph Nodes

Sabine Stoll,1 Jérôme Delon,1 Tilmann M. Brotz,2* Ronald N. Germain1dagger

T cell immune responses begin within organized lymphoid tissues. The pace, topology, and outcomes of the cellular interactions that underlie these responses have, so far, been inferred from static imaging of sectioned tissue or from studies of cultured cells. Here we report dynamic visualization of antigen-specific T cells interacting with dendritic cells within intact explanted lymph nodes. We observed immunological synapse formation and prolonged interactions between these two cell types, followed by the activation, dissociation, and rapid migration of T cells away from the antigenic stimulus. This high-resolution spatiotemporal analysis provides insight into the nature of cell interactions critical to early immune responses within lymphoid structures.

1 Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health,
2 Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
*   Present address: 270 Littlefield Avenue, South San Francisco, CA 94080, USA.

dagger    To whom correspondence should be addressed. E-mail: rgermain{at}nih.gov

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
CCL21 mediates CD4+ T-cell costimulation via a DOCK2/Rac-dependent pathway.
K. Gollmer, F. Asperti-Boursin, Y. Tanaka, K. Okkenhaug, B. Vanhaesebroeck, J. R. Peterson, Y. Fukui, E. Donnadieu, and J. V. Stein (2009)
Blood 114, 580-588
   Abstract »    Full Text »    PDF »
B7-H1 (PD-L1) on T cells is required for T-cell-mediated conditioning of dendritic cell maturation.
O. Talay, C.-H. Shen, L. Chen, and J. Chen (2009)
PNAS 106, 2741-2746
   Abstract »    Full Text »    PDF »
Asymmetric Division and Stem Cell Renewal without a Permanent Niche: Lessons from Lymphocytes.
J.T. Chang and S.L. Reiner (2008)
Cold Spring Harb Symp Quant Biol
   Abstract »    PDF »
Mesenchymal Stem Cells Alter Migratory Property of T and Dendritic Cells to Delay the Development of Murine Lethal Acute Graft-Versus-Host Disease.
H. Li, Z. Guo, X. Jiang, H. Zhu, X. Li, and N. Mao (2008)
Stem Cells 26, 2531-2541
   Abstract »    Full Text »    PDF »
Apoptotic Cells Induce Immunosuppression through Dendritic Cells: Critical Roles of IFN-{gamma} and Nitric Oxide.
G. Ren, J. Su, X. Zhao, L. Zhang, J. Zhang, A. I. Roberts, H. Zhang, G. Das, and Y. Shi (2008)
J. Immunol. 181, 3277-3284
   Abstract »    Full Text »    PDF »
How Antigen Quantity and Quality Determine T-Cell Decisions in Lymphoid Tissue.
H. Zheng, B. Jin, S. E. Henrickson, A. S. Perelson, U. H. von Andrian, and A. K. Chakraborty (2008)
Mol. Cell. Biol. 28, 4040-4051
   Abstract »    Full Text »    PDF »
Osteoimmunology: Interactions of the Bone and Immune System.
J. Lorenzo, M. Horowitz, and Y. Choi (2008)
Endocr. Rev. 29, 403-440
   Abstract »    Full Text »    PDF »
Tumor Escape Mechanism Governed by Myeloid-Derived Suppressor Cells.
S. Nagaraj and D. I. Gabrilovich (2008)
Cancer Res. 68, 2561-2563
   Abstract »    Full Text »    PDF »
Prevention of acute graft-versus-host disease by blocking T-cell entry to secondary lymphoid organs.
A. Beilhack, S. Schulz, J. Baker, G. F. Beilhack, R. Nishimura, E. M. Baker, G. Landan, E. I. Herman, E. C. Butcher, C. H. Contag, et al. (2008)
Blood 111, 2919-2928
   Abstract »    Full Text »    PDF »
How polarity shapes the destiny of T cells.
S. Russell (2008)
J. Cell Sci. 121, 131-136
   Abstract »    Full Text »    PDF »
Calmodulin-dependent kinase IV links Toll-like receptor 4 signaling with survival pathway of activated dendritic cells.
M. Illario, M. L. Giardino-Torchia, U. Sankar, T. J. Ribar, M. Galgani, L. Vitiello, A. M. Masci, F. R. Bertani, E. Ciaglia, D. Astone, et al. (2008)
Blood 111, 723-731
   Abstract »    Full Text »    PDF »
Bidirectional MHC molecule exchange between migratory and resident dendritic cells.
M. de Heusch, D. Blocklet, D. Egrise, B. Hauquier, M. Vermeersch, S. Goldman, and M. Moser (2007)
J. Leukoc. Biol. 82, 861-868
   Abstract »    Full Text »    PDF »
Adhesion and Degranulation-Promoting Adapter Protein (ADAP) Positively Regulates T Cell Sensitivity to Antigen and T Cell Survival.
K. L. Mueller, M. S. Thomas, B. J. Burbach, E. J. Peterson, and Y. Shimizu (2007)
J. Immunol. 179, 3559-3569
   Abstract »    Full Text »    PDF »
The Role of B Cells in the Development of CD4 Effector T Cells during a Polarized Th2 Immune Response.
Q. Liu, Z. Liu, C. T. Rozo, H. A. Hamed, F. Alem, J. F. Urban Jr., and W. C. Gause (2007)
J. Immunol. 179, 3821-3830
   Abstract »    Full Text »    PDF »
Real-time Imaging of Tumor-Cell Shedding and Trafficking in Lymphatic Channels.
K. Hayashi, P. Jiang, K. Yamauchi, N. Yamamoto, H. Tsuchiya, K. Tomita, A.R. Moossa, M. Bouvet, and R. M. Hoffman (2007)
Cancer Res. 67, 8223-8228
   Abstract »    Full Text »    PDF »
IL-10 permits transient activation of dendritic cells to tolerize T cells and protect from central nervous system autoimmune disease.
G. Perona-Wright, S. M. Anderton, S. E. M. Howie, and D. Gray (2007)
Int. Immunol. 19, 1123-1134
   Abstract »    Full Text »    PDF »
Ca2+ Signals in CD4+ T Cells during Early Contacts with Antigen-Bearing Dendritic Cells in Lymph Node.
S. H. Wei, O. Safrina, Y. Yu, K. R. Garrod, M. D. Cahalan, and I. Parker (2007)
J. Immunol. 179, 1586-1594
   Abstract »    Full Text »    PDF »
Sequential Activation of CD8+ T Cells in the Draining Lymph Nodes in Response to Pulmonary Virus Infection.
H. Yoon, K. L. Legge, S.-s. J. Sung, and T. J. Braciale (2007)
J. Immunol. 179, 391-399
   Abstract »    Full Text »    PDF »
MHC class II deprivation impairs CD4 T cell motility and responsiveness to antigen-bearing dendritic cells in vivo.
U. B. Fischer, E. L. Jacovetty, R. B. Medeiros, B. D. Goudy, T. Zell, J.-B. Swanson, E. Lorenz, Y. Shimizu, M. J. Miller, A. Khoruts, et al. (2007)
PNAS 104, 7181-7186
   Abstract »    Full Text »    PDF »
Asymmetric T Lymphocyte Division in the Initiation of Adaptive Immune Responses.
J. T. Chang, V. R. Palanivel, I. Kinjyo, F. Schambach, A. M. Intlekofer, A. Banerjee, S. A. Longworth, K. E. Vinup, P. Mrass, J. Oliaro, et al. (2007)
Science 315, 1687-1691
   Abstract »    Full Text »    PDF »
Competition for antigen determines the stability of T cell-dendritic cell interactions during clonal expansion.
Z. Garcia, E. Pradelli, S. Celli, H. Beuneu, A. Simon, and P. Bousso (2007)
PNAS 104, 4553-4558
   Abstract »    Full Text »    PDF »
T-cell-receptor-dependent actin regulatory mechanisms.
Y. Huang and J. K. Burkhardt (2007)
J. Cell Sci. 120, 723-730
   Abstract »    Full Text »    PDF »
In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor.
A. Boissonnas, L. Fetler, I. S. Zeelenberg, S. Hugues, and S. Amigorena (2007)
J. Exp. Med. 204, 345-356
   Abstract »    Full Text »    PDF »
Loss of Src Homology Region 2 Domain-Containing Protein Tyrosine Phosphatase-1 Increases CD8+ T Cell-APC Conjugate Formation and Is Associated with Enhanced In Vivo CTL Function.
J. G. Sathish, G. Dolton, F. G. LeRoy, and R. J. Matthews (2007)
J. Immunol. 178, 330-337
   Abstract »    Full Text »    PDF »
HIV interactions with dendritic cells: has our focus been too narrow?.
H. Donaghy, J. Wilkinson, and A. L. Cunningham (2006)
J. Leukoc. Biol. 80, 1001-1012
   Abstract »    Full Text »    PDF »
Aberrant Phenotype and Function of Myeloid Dendritic Cells in Systemic Lupus Erythematosus.
D. Ding, H. Mehta, W. J. McCune, and M. J. Kaplan (2006)
J. Immunol. 177, 5878-5889
   Abstract »    Full Text »    PDF »
Normal Structure, Function, and Histology of Lymph Nodes.
C. L. Willard-Mack (2006)
Toxicol Pathol 34, 409-424
   Abstract »    Full Text »    PDF »
Extrafollicular activation of lymph node B cells by antigen-bearing dendritic cells..
H. Qi, J. G. Egen, A. Y. C. Huang, and R. N. Germain (2006)
Science 312, 1672-1676
   Abstract »    Full Text »    PDF »
CD4+ T cell-independent maintenance and expansion of memory CD8+ T cells derived from in vitro dendritic cell activation.
M. Shi and J. Xiang (2006)
Int. Immunol. 18, 887-895
   Abstract »    Full Text »    PDF »
Activation of thymic T cells by MHC alloantigen requires syngeneic, activated CD4+ T cells and B cells as APC.
T. M Strutt, J. Uzonna, K. K McKinstry, and P. A Bretscher (2006)
Int. Immunol. 18, 719-728
   Abstract »    Full Text »    PDF »
Regulatory T cells inhibit stable contacts between CD4+ T cells and dendritic cells in vivo.
C. E. Tadokoro, G. Shakhar, S. Shen, Y. Ding, A. C. Lino, A. Maraver, J. J. Lafaille, and M. L. Dustin (2006)
J. Exp. Med. 203, 505-511
   Abstract »    Full Text »    PDF »
An Essential Role of Antigen-Presenting Cell/T-Helper Type 1 Cell-Cell Interactions in Draining Lymph Node during Complete Eradication of Class II-Negative Tumor Tissue by T-Helper Type 1 Cell Therapy.
K. Chamoto, D. Wakita, Y. Narita, Y. Zhang, D. Noguchi, H. Ohnishi, T. Iguchi, T. Sakai, H. Ikeda, and T. Nishimura (2006)
Cancer Res. 66, 1809-1817
   Abstract »    Full Text »    PDF »
Bone Marrow-Derived Dendritic Cells Reverse the Anergic State of CD4+CD25+ T Cells without Reversing Their Suppressive Function.
C. Brinster and E. M. Shevach (2005)
J. Immunol. 175, 7332-7340
   Abstract »    Full Text »    PDF »
Innate control of adaptive immunity via remodeling of lymph node feed arteriole.
K. A. Soderberg, G. W. Payne, A. Sato, R. Medzhitov, S. S. Segal, and A. Iwasaki (2005)
PNAS 102, 16315-16320
   Abstract »    Full Text »    PDF »
CD4 T cells integrate signals delivered during successive DC encounters in vivo.
S. Celli, Z. Garcia, and P. Bousso (2005)
J. Exp. Med. 202, 1271-1278
   Abstract »    Full Text »    PDF »
The c-SMAC: sorting it all out (or in).
J. Lin, M. J. Miller, and A. S. Shaw (2005)
J. Cell Biol. 170, 177-182
   Abstract »    Full Text »    PDF »
Importance of integrin LFA-1 deactivation for the generation of immune responses.
M. Semmrich, A. Smith, C. Feterowski, S. Beer, B. Engelhardt, D. H. Busch, B. Bartsch, M. Laschinger, N. Hogg, K. Pfeffer, et al. (2005)
J. Exp. Med. 201, 1987-1998
   Abstract »    Full Text »    PDF »
T Cells in G1 Provide a Memory-Like Response to Secondary Stimulation.
I. Munitic, P. E. Ryan, and J. D. Ashwell (2005)
J. Immunol. 174, 4010-4018
   Abstract »    Full Text »    PDF »
Naive, Effector, and Memory T Lymphocytes Efficiently Scan Dendritic Cells In Vivo: Contact Frequency in T Cell Zones of Secondary Lymphoid Organs Does Not Depend on LFA-1 Expression and Facilitates Survival of Effector T Cells.
J. Westermann, U. Bode, A. Sahle, U. Speck, N. Karin, E. B. Bell, K. Kalies, and A. Gebert (2005)
J. Immunol. 174, 2517-2524
   Abstract »    Full Text »    PDF »
Movies, measurement, and modeling: the three Ms of mechanistic immunology.
C. Witt, S. Raychaudhuri, and A. K. Chakraborty (2005)
J. Exp. Med. 201, 501-504
   Abstract »    Full Text »    PDF »
Dynamic Multiphoton Imaging: A Live View from Cells to Systems.
G. E. Stutzmann and I. Parker (2005)
Physiology 20, 15-21
   Abstract »    Full Text »    PDF »
Following Immunization Antigen Becomes Concentrated in a Limited Number of APCs Including B Cells.
C. A. Byersdorfer, R. J. DiPaolo, S. J. Petzold, and E. R. Unanue (2004)
J. Immunol. 173, 6627-6634
   Abstract »    Full Text »    PDF »
A spectrum of biophysical interaction modes between T cells and different antigen-presenting cells during priming in 3-D collagen and in vivo.
M. Gunzer, C. Weishaupt, A. Hillmer, Y. Basoglu, P. Friedl, K. E. Dittmar, W. Kolanus, G. Varga, and S. Grabbe (2004)
Blood 104, 2801-2809
   Abstract »    Full Text »    PDF »
Manipulating dendritic cell biology for the active immunotherapy of cancer.
D. W. O'Neill, S. Adams, and N. Bhardwaj (2004)
Blood 104, 2235-2246
   Abstract »    Full Text »    PDF »
Imaging the Single Cell Dynamics of CD4+ T Cell Activation by Dendritic Cells in Lymph Nodes.
M. J. Miller, O. Safrina, I. Parker, and M. D. Cahalan (2004)
J. Exp. Med. 200, 847-856
   Abstract »    Full Text »    PDF »
Strong and Durable TCR Clustering at the T/Dendritic Cell Immune Synapse Is Not Required for NFAT Activation and IFN-{gamma} Production in Human CD4+ T Cells.
N. Blanchard, M. Decraene, K. Yang, F. Miro-Mur, S. Amigorena, and C. Hivroz (2004)
J. Immunol. 173, 3062-3072
   Abstract »    Full Text »    PDF »
Higher Prostaglandin E2 Production by Dendritic Cells from Subjects with Asthma Compared with Normal Subjects.
J. A. Long, M. Fogel-Petrovic, D. A. Knight, P. J. Thompson, and J. W. Upham (2004)
Am. J. Respir. Crit. Care Med. 170, 485-491
   Abstract »    Full Text »    PDF »
Cutting Edge: Membrane Nanotubes Connect Immune Cells.
B. Onfelt, S. Nedvetzki, K. Yanagi, and D. M. Davis (2004)
J. Immunol. 173, 1511-1513
   Abstract »    Full Text »    PDF »
Antigen-Specific Lymphocyte Sequestration in Lymphoid Organs: Lack of Essential Roles for {alpha}L and {alpha}4 Integrin-Dependent Adhesion or G{alpha}i Protein-Coupled Receptor Signaling.
C. N. Arnold, E. C. Butcher, and D. J. Campbell (2004)
J. Immunol. 173, 866-873
   Abstract »    Full Text »    PDF »
Expression Characteristics and Stimulatory Functions of CD43 in Human CD4+ Memory T Cells: Analysis Using a Monoclonal Antibody to CD43 That Has a Novel Lineage Specificity.
S. Kyoizumi, T. Ohara, Y. Kusunoki, T. Hayashi, K. Koyama, and N. Tsuyama (2004)
J. Immunol. 172, 7246-7253
   Abstract »    Full Text »    PDF »
Antigen Location Contributes to the Pathological Features of a Transplanted Heart Graft.
Y. Chen, Y. Demir, A. Valujskikh, and P. S. Heeger (2004)
Am. J. Pathol. 164, 1407-1415
   Abstract »    Full Text »    PDF »
IL-4-mediated inhibition of IFN-{gamma} production by CD4+ T cells proceeds by several developmentally regulated mechanisms.
O. Wurtz, M. Bajenoff, and S. Guerder (2004)
Int. Immunol. 16, 501-508
   Abstract »    Full Text »    PDF »
Spontaneous Organ-Specific Th2-Mediated Autoimmunity in TCR Transgenic Mice.
S. Candon, R. S. McHugh, G. Foucras, K. Natarajan, E. M. Shevach, and D. H. Margulies (2004)
J. Immunol. 172, 2917-2924
   Abstract »    Full Text »    PDF »
T cell repertoire scanning is promoted by dynamic dendritic cell behavior and random T cell motility in the lymph node.
M. J. Miller, A. S. Hejazi, S. H. Wei, M. D. Cahalan, and I. Parker (2004)
PNAS 101, 998-1003
   Abstract »    Full Text »    PDF »
Antigen-Specific Inhibition of CD8+ T Cell Response by Immature Myeloid Cells in Cancer Is Mediated by Reactive Oxygen Species.
S. Kusmartsev, Y. Nefedova, D. Yoder, and D. I. Gabrilovich (2004)
J. Immunol. 172, 989-999
   Abstract »    Full Text »    PDF »
NK Cell TRAIL Eliminates Immature Dendritic Cells In Vivo and Limits Dendritic Cell Vaccination Efficacy.
Y. Hayakawa, V. Screpanti, H. Yagita, A. Grandien, H.-G. Ljunggren, M. J. Smyth, and B. J. Chambers (2004)
J. Immunol. 172, 123-129
   Abstract »    Full Text »    PDF »
Dendritic Cell Maturation Controls Adhesion, Synapse Formation, and the Duration of the Interactions with Naive T Lymphocytes.
F. Benvenuti, C. Lagaudriere-Gesbert, I. Grandjean, C. Jancic, C. Hivroz, A. Trautmann, O. Lantz, and S. Amigorena (2004)
J. Immunol. 172, 292-301
   Abstract »    Full Text »    PDF »
Cutting Edge: Dendritic Cell Actin Cytoskeletal Polarization during Immunological Synapse Formation Is Highly Antigen-Dependent.
M. M. Al-Alwan, R. S. Liwski, S. M. M. Haeryfar, W. H. Baldridge, D. W. Hoskin, G. Rowden, and K. A. West (2003)
J. Immunol. 171, 4479-4483
   Abstract »    Full Text »    PDF »
The Strategy of T Cell Antigen-presenting Cell Encounter in Antigen-draining Lymph Nodes Revealed by Imaging of Initial T Cell Activation.
M. Bajenoff, S. Granjeaud, and S. Guerder (2003)
J. Exp. Med. 198, 715-724
   Abstract »    Full Text »    PDF »
Cutting Edge: T Lymphocyte Activation by Repeated Immunological Synapse Formation and Intermittent Signaling.
M. Faroudi, R. Zaru, P. Paulet, S. Muller, and S. Valitutti (2003)
J. Immunol. 171, 1128-1132
   Abstract »    Full Text »    PDF »
Dendritic Cells Are Responsible for the Capacity of CpG Oligodeoxynucleotides to Act as an Adjuvant for Protective Vaccine Immunity Against Leishmania major in Mice.
J. A. Shah, P. A. Darrah, D. R. Ambrozak, T. N. Turon, S. Mendez, J. Kirman, C.-Y. Wu, N. Glaichenhaus, and R. A. Seder (2003)
J. Exp. Med. 198, 281-291
   Abstract »    Full Text »    PDF »
Restricted Clonal Expression of IL-2 By Naive T Cells Reflects Differential Dynamic Interactions with Dendritic Cells.
V. Hurez, A. Saparov, A. Tousson, M. J. Fuller, T. Kubo, J. Oliver, B. T. Weaver, and C. T. Weaver (2003)
J. Exp. Med. 198, 123-132
   Abstract »    Full Text »    PDF »
Critical Impact of the Kinetics of Dendritic Cells Activation on the in Vivo Induction of Tumor-specific T Lymphocytes.
A. Camporeale, A. Boni, G. Iezzi, E. Degl'Innocenti, M. Grioni, A. Mondino, and M. Bellone (2003)
Cancer Res. 63, 3688-3694
   Abstract »    Full Text »    PDF »
Low T cell receptor expression and thermal fluctuations contribute to formation of dynamic multifocal synapses in thymocytes.
S.-J. E. Lee, Y. Hori, and A. K. Chakraborty (2003)
PNAS 100, 4383-4388
   Abstract »    Full Text »    PDF »
Dendritic Cell Responses to Early Murine Cytomegalovirus Infection: Subset Functional Specialization and Differential Regulation by Interferon {alpha}/{beta}.
M. Dalod, T. Hamilton, R. Salomon, T. P. Salazar-Mather, S. C. Henry, J. D. Hamilton, and C. A. Biron (2003)
J. Exp. Med. 197, 885-898
   Abstract »    Full Text »    PDF »
The Size of the Synaptic Cleft and Distinct Distributions of Filamentous Actin, Ezrin, CD43, and CD45 at Activating and Inhibitory Human NK Cell Immune Synapses.
F. E. McCann, B. Vanherberghen, K. Eleme, L. M. Carlin, R. J. Newsam, D. Goulding, and D. M. Davis (2003)
J. Immunol. 170, 2862-2870
   Abstract »    Full Text »    PDF »
Autonomous T cell trafficking examined in vivo with intravital two-photon microscopy.
M. J. Miller, S. H. Wei, M. D. Cahalan, and I. Parker (2003)
PNAS 100, 2604-2609
   Abstract »    Full Text »    PDF »
Inducible Costimulatory Molecule-B7-Related Protein 1 Interactions Are Important for the Clonal Expansion and B Cell Helper Functions of Naive, Th1, and Th2 T Cells.
K. M. Smith, J. M. Brewer, P. Webb, A. J. Coyle, C. Gutierrez-Ramos, and P. Garside (2003)
J. Immunol. 170, 2310-2315
   Abstract »    Full Text »    PDF »
Dynamic Changes During the Immune Response in T Cell-Antigen-presenting Cell Clusters Isolated from Lymph Nodes.
M. Hommel and B. Kyewski (2003)
J. Exp. Med. 197, 269-280
   Abstract »    Full Text »    PDF »
Cutting Edge: L-Selectin (CD62L) Expression Distinguishes Small Resting Memory CD4+ T Cells That Preferentially Respond to Recall Antigen.
R. L. Hengel, V. Thaker, M. V. Pavlick, J. A. Metcalf, G. Dennis Jr., J. Yang, R. A. Lempicki, I. Sereti, and H. C. Lane (2003)
J. Immunol. 170, 28-32
   Abstract »    Full Text »    PDF »
Neural and Immunological Synaptic Relations.
M. L. Dustin and D. R. Colman (2002)
Science 298, 785-789
   Abstract »    Full Text »    PDF »
Antigen Presentation by Dendritic Cells In Vivo.
E. Mougneau, S. Hugues, and N. Glaichenhaus (2002)
J. Exp. Med. 196, 1013-1016
   Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)