Abstract
T cell activation is crucial for the development of specific immune reactions. It requires physical contact between T cells and antigen-presenting cells (APC). Since these cells are initially located at distinct positions in the body, they have to migrate and find each other within secondary lymphoid organs. After encountering each other both cells have to maintain a close membrane contact sufficiently long to ensure successful signaling. Thus, there is the necessity to temporarily synchronize the motile behavior of these cells. Initially, it had been proposed that during antigen recognition, T cells receive a stop signal and maintain a stable contact with APC for several hours when an appropriate APC has been encountered. However, direct cell observation via time-lapse microscopy in vitro and in vivo has revealed a different picture. While long contacts can be observed, many interactions appear to be very short and sequential despite efficient signaling. Thus, two concepts addressing the biophysics of T cell activation have emerged. The single encounter model proposes that after a period of dynamic searching, a T cell stops to interact with one appropriately presenting APC until signaling is completed. The serial encounter model suggests that T cells are able to collect a series of short signals by different APC until a critical activation threshold is achieved. Future research needs to clarify the relative importance of short and dynamic versus long-lived T cell–APC encounters for the outcome of T cell activation. Furthermore, a thorough understanding of the molecular events underlying the observed complex motility patterns will make these phenomena amenable for intervention, which might result in the identification of new types of immune modulating drugs.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Alberola-Ila J et al. (1995) Selective requirement for MAP kinase activation in thymocyte differentiation. Nature 373(6515):620–623
Bajenoff M, Granjeaud S, Guerder S (2003) The strategy of T cell antigen-presenting cell encounter in antigen-draining lymph nodes revealed by imaging of initial T cell activation. J Exp Med 198(5):715–724
Bhakta NR, Oh DY, Lewis RS (2005) Calcium oscillations regulate thymocyte motility during positive selection in the three-dimensional thymic environment. Nat Immunol 6(2):143–151
Borovsky Z et al. (2002) Serial triggering of T cell receptors results in incremental accumulation of signaling intermediates. J Biol Chem 277(24):21529–21536
Bousso P et al. (2002) Dynamics of thymocyte–stromal cell interactions visualized by two-photon microscopy. Science 296(5574):1876–1880
Bradley LM, Watson SR (1996) Lymphocyte migration into tissue: the paradigm derived from CD4 subsets. Curr Opin Immunol 8(3):312–320
Brocker T (1997) Survival of mature CD4 T lymphocytes is dependent on major histocompatibility complex class-II expressing dendritic cells. J Exp Med 186(8):1223–1232
Butcher EC, Picker LJ (1996) Lymphocyte homing and homeostasis. Science 272(5258):60–66
Cella M et al. (1997) Inflammatory stimuli induce accumulation of MHC class II complexes on dendritic cells. Nature 388(6644):782–787
Correia-Neves M et al. (2001) The shaping of the T cell repertoire. Immunity 14(1):21–32
Dustin ML, Chan AC (2000) Signaling takes shape in the immune system. Cell 103(2):283–294
Dustin ML, de Fougerolles AR (2001) Reprogramming T cells: the role of extracellular matrix in coordination of T cell activation and migration. Curr Opin Immunol 13(3):286–290
Dustin ML et al. (1997) Antigen receptor engagement delivers a stop signal to migrating T lymphocytes. Proc Natl Acad Sci USA 94(8):3909–3913
Dustin ML, Allen PM, Shaw AS (2001) Environmental control of immunological synapse formation and duration. Trends Immunol 22(4):192–194
Faroudi M et al. (2003) Cutting edge: T lymphocyte activation by repeated immunological synapse formation and intermittent signaling. J Immunol 171(3):1128–1132
Fontenot JD et al. (2005) Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 22(3):329–341
Forster R et al. (1999) CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell 99(1):23–33
Friedl P, Brocker EB (2002) TCR triggering on the move: diversity of T cell interactions with antigen-presenting cells. Immunol Rev 186:83–89
Friedl P, Gunzer M (2001) Interaction of T cells with APCs: the serial encounter model. Trends Immunol 22(4):187–191
Friedl P et al. (1994) Locomotor phenotypes of unstimulated CD45RAhigh and CD45ROhigh CD4+ and CD8+ lymphocytes in three-dimensional collagen lattices. Immunology 82(4):617–624
Friedl P, Noble PB, Zanker KS (1995) T lymphocyte locomotion in a three-dimensional collagen matrix. Expression and function of cell adhesion molecules. J Immunol 154(10):4973–4985
Friedl P et al. (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(8):2331–2343
Fuchs EJ, Matzinger P (1992) B cells turn off virgin but not memory T cells. Science 258(5085):1156–1159
Germain RN, Jenkins MK (2004) In vivo antigen presentation. Curr Opin Immunol 16(1):120–125
Goldrath AW, Bevan MJ (1999) Selecting and maintaining a diverse T cell repertoire. Nature 402(6759):255–262
Gretz JE, Anderson AO, Shaw S (1997) Cords, channels, corridors and conduits: critical architectural elements facilitating cell interactions in the lymph node cortex. Immunol Rev 156:11–24
Gretz JE et al. (2000) 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(10):1425–1440
Gunzer M et al. (2000) Antigen presentation in extracellular matrix: interactions of T cells with dendritic cells are dynamic, short lived, and sequential. Immunity 13(3):323–332
Gunzer M et al. (2004) A spectrum of biophysical interaction modes between T cells and different antigen-presenting cells during priming in 3D collagen and in vivo. Blood 104(9):2801–2809
Gunzer M et al. (2005) Systemic administration of a TLR7 ligand leads to transient immune incompetence due to peripheral-blood leukocyte depletion. Blood 106(7):2424–2432
Hugues S et al. (2004) Distinct T cell dynamics in lymph nodes during the induction of tolerance and immunity. Nat Immunol 5(12):1235–1242
Hurez V et al. (2003) Restricted clonal expression of IL-2 by naive T cells reflects differential dynamic interactions with dendritic cells. J Exp Med 198(1):123–132
Hwang JM et al. (2004) A critical temporal window for selectin-dependent CD4+ lymphocyte homing and initiation of late-phase inflammation in contact sensitivity. J Exp Med 199(9):1223–1234
Iezzi G, Karjalainen K, Lanzavecchia A (1998) The duration of antigenic stimulation determines the fate of naive and effector T cells. Immunity 8(1):89–95
Irvine DJ, Purbhoo MA, Krogsgaard M, Davis MM (2002) Direct observation of ligand recognition by T cells. Nature 419(6909):845–849
Itano AA et al. (2003) Distinct dendritic cell populations sequentially present antigen to CD4 T cells and stimulate different aspects of cell-mediated immunity. Immunity 19(1):47–57
Jonuleit H et al. (2001) Identification and functional characterization of human CD4(+)CD25(+) T cells with regulatory properties isolated from peripheral blood. J Exp Med 193(11):1285–1294
Kaldjian EP et al. (2001) Spatial and molecular organization of lymph node T cell cortex: a labyrinthine cavity bounded by an epithelium-like monolayer of fibroblastic reticular cells anchored to basement membrane-like extracellular matrix. Int Immunol 13(10):1243–1253
Kannagi R (2002) Regulatory roles of carbohydrate ligands for selectins in the homing of lymphocytes. Curr Opin Struct Biol 12(5):599–608
Kedl RM et al. (2000) T cells compete for access to antigen-bearing antigen-presenting cells. J Exp Med 192(8):1105–1113
Kupfer A, Singer SJ (1989) The specific interaction of helper T cells and antigen-presenting B cells. IV. Membrane and cytoskeletal reorganizations in the bound T cell as a function of antigen dose. J Exp Med 170(5):1697–1713
Lanzavecchia A, Sallusto F (2001) Antigen decoding by T lymphocytes: from synapses to fate determination. Nat Immunol 2(6):487–492
Lanzavecchia A, Lezzi G, Viola A (1999) From TCR engagement to T cell activation: a kinetic view of T cell behavior. Cell 96(1):1–4
Lee KH et al. (2002) T cell receptor signaling precedes immunological synapse formation. Science 295(5559):1539–1542
Lee KH et al. (2003) The immunological synapse balances T cell receptor signaling and degradation. Science 302(5648):1218–1222
Lindquist RL et al. (2004) Visualizing dendritic cell networks in vivo. Nat Immunol 5(12):1243–1250
Lukas M et al. (1996) Human cutaneous dendritic cells migrate through dermal lymphatic vessels in a skin organ culture model. J Invest Dermatol 106(6):1293–1299
Mackay CR (1993) Homing of naive, memory and effector lymphocytes. Curr Opin Immunol 5(3):423–427
Mehling A et al. (2001) Overexpression of CD40 ligand in murine epidermis results in chronic skin inflammation and systemic autoimmunity. J Exp Med 194(5):615–628
Mellman I, Steinman RM (2001) qDendritic cells: specialized and regulated antigen processing machines. Cell 106(3):255–258
Mempel TR, Henrickson SE, Von Andrian UH (2004) T cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature 427(6970):154–159
Miller MJ et al. (2002) Two-photon imaging of lymphocyte motility and antigen response in intact lymph node. Science 296(5574):1869–1873
Miller MJ et al. (2003) Autonomous T cell trafficking examined in vivo with intravital two-photon microscopy. Proc Natl Acad Sci USA 100(5):2604–2609
Miller MJ et al. (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(4):998–1003
Miller MJ et al. (2004b) Imaging the single cell dynamics of CD4+ T cell activation by dendritic cells in lymph nodes. J Exp Med 200(7):847–856
Monks CR et al. (1998) Three-dimensional segregation of supramolecular activation clusters in T cells. Nature 395(6697):82–86
Moser B, Loetscher P (2001) Lymphocyte traffic control by chemokines. Nat Immunol 2(2):123–128
Negulescu PA et al. (1996) Polarity of T cell shape, motility, and sensitivity to antigen. Immunity 4(5):421–430
Nikolich-Zugich J, Slifka MK, Messaoudi I (2004) The many important facets of T-cell repertoire diversity. Nat Rev Immunol 4(2):123–132
Okada T et al. (2005) Antigen-engaged B cells undergo chemotaxis toward the T zone, form motile conjugates with helper T cells. PLoS Biol 3(6):e150
O'Neill EJ et al. (2004) Natural and induced regulatory T cells. Ann NY Acad Sci 1029(1):180–192
Palmer E (2003) Negative selection—clearing out the bad apples from the T cell repertoire. Nat Rev Immunol 3(5):383–391
Potsch C, Vohringer D, Pircher H (1999) Distinct migration patterns of naive and effector CD8 T cells in the spleen: correlation with CCR7 receptor expression and chemokine reactivity. Eur J Immunol 29(11):3562–3570
Probst HC et al. (2003) Inducible transgenic mice reveal resting dendritic cells as potent inducers of CD8+ T cell tolerance. Immunity 18(5):713–720
Rachmilewitz J, Lanzavecchia A (2002) A temporal and spatial summation model for T cell activation: signal integration and antigen decoding. Trends Immunol 23(12):592–595
Reif K et al. (2002) Balanced responsiveness to chemoattractants from adjacent zones determines B cell position. Nature 416:94–99
Richie LI et al. (2002) Imaging synapse formation during thymocyte selection: inability of CD3zeta to form a stable central accumulation during negative selection. Immunity 16(4):595–606
Rodriguez-Pinto D, Moreno JB (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(4):1097–1105
Romani N et al. (2001) Migration of dendritic cells into lymphatics—the Langerhans cell example: routes, regulation, and relevance. Int Rev Cytol 207:237–270
Rosette C et al. (2001) The impact of duration versus extent of TCR occupancy on T cell activation: a revision of the kinetic proofreading model. Immunity 15(1):59–70
Sakaguchi S (2005) Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol 6(4):345–352
Sallusto F et al. (1999) Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401(6754):708–712
Sallusto F, Geginat J, Lanzavecchia A (2004) Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol 22(1):745–763
Sebzda E et al. (1999) Selection of the T cell repertoire. Annu Rev Immunol 17(1):829–874
Seder RA, Ahmed R (2003) Similarities and differences in CD4+ and CD8+ effector and memory T cell generation. Nat Immunol 4(9):835–842
Shakhar G et al. (2005) Stable T cell–dendritic cell interactions precede the development of both tolerance and immunity in vivo. Nat Immunol 6(7):707–714
Springer TA (1990) Adhesion receptors of the immune system. Nature 346(6283):425–434
Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76(2):301–314
Stoll S, Delon J, Brotz TM, Germain RN (2002) Dynamic imaging of T cell–dendritic cell interactions in lymph nodes. Science 296(5574):1873–1876
Underhill DM et al. (1999) Dynamic interactions of macrophages with T cells during antigen presentation. J Exp Med 190(12):1909–1914
Ushiki T, Ohtani O, Abe K (1995) Scanning electron microscopic studies of reticular framework in the rat mesenteric lymph node. Anat Rec 241(1):113–122
Valitutti S et al. (1995) Sustained signaling leading to T cell activation results from prolonged T cell receptor occupancy. Role of T cell actin cytoskeleton. J Exp Med 181:577–584
Wei SH et al. (2003) A stochastic view of lymphocyte motility and trafficking within the lymph node. Immunol Rev 195:136–159
Westermann J et al. (2005) 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 Immunol 174(5):2517-2524
Witt CM et al. (2005) Directed migration of positively selected thymocytes visualized in real time. PLoS Biol 3(6):e160
Yasutomo K et al. (2000) The duration of antigen receptor signalling determines CD4+ versus CD8+ T-cell lineage fate. Nature 404(6777):506–510
Author information
Authors and Affiliations
Corresponding author
Editor information
Rights and permissions
Copyright information
© 2006 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Reichardt, P., Gunzer, M. (2006). The Biophysics of T Lymphocyte Activation In Vitro and In Vivo. In: Gundelfinger, E.D., Seidenbecher, C.I., Schraven, B. (eds) Cell Communication in Nervous and Immune System. Results and Problems in Cell Differentiation, vol 43. Springer, Berlin, Heidelberg . https://doi.org/10.1007/400_021
Download citation
DOI: https://doi.org/10.1007/400_021
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-36828-1
Online ISBN: 978-3-540-36829-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)