Modeling Migration, Compartmentalization and Exit of Naive T Cells in Lymph Nodes Without Chemotaxis

  • Johannes Textor
  • Jürgen Westermann
Conference paper
Part of the Lecture Notes in Computer Science book series (LNCS, volume 4628)

Abstract

The migration of lymphocytes through secondary lymphoid organs was believed to be mainly controlled by chemokine gradients. This theory has recently been called into question since naive lymphocytes observed in vivo by two-photon microscopy show no evidence of directed migration. We have constructed a simple mathematical model of naive T cell migration in lymph nodes that is solely based on local mechanisms. The model was validated against findings from histological analysis and experimentally determined lymphocyte recirculation kinetics. Our results suggest that T cell compartmentalization in lymph nodes can be explained without long-range chemokine gradients. However, the T cell residence time predicted by our model is significantly lower than observed in vivo, indicating the existence of a mechanism which alters the T cell random walk over time.

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References

  1. 1.
    Westermann, J., Pabst, R.: Distribution of Lymphocyte Subsets and Natural Killer Cells in the Human Body. Clin. Investig. 70, 539–544 (1992)CrossRefGoogle Scholar
  2. 2.
    Von Andrian, U.H., Mackay, C.R.: T-Cell Function and Migration. Two Sides of the Same Coin. N. Engl. J. Med. 343(14), 1020–1032 (2000)Google Scholar
  3. 3.
    Moser, B., Loetscher, P.: Lymphocyte Traffic Control by Chemokines. Nat. Immunol. 2(2), 123–128 (2001)CrossRefGoogle Scholar
  4. 4.
    Reif, K., Ekland, E.H., Ohl, L., Nakano, H., Lipp, M., Förster, R., Cyster, J.G.: Balanced Responsiveness to Chemoattractants from Adjacent Zones Determines B-Cell Position. Nature 416, 94–99 (2002)CrossRefGoogle Scholar
  5. 5.
    Cyster, J.G., Ansel, K.M., Reif, K., Ekland, E.H., Hyman, P., Tang, H.L., Luther, S.A., Ngo, V.N.: Follicular Stromal Cells and Lymphocyte Homing to Follicles. Immunol. Rev. 176, 181–193 (2000)CrossRefGoogle Scholar
  6. 6.
    Westermann, J., Engelhardt, B., Hoffmann, J.: Migration of T Cells In Vivo: Molecular Mechanisms and Clinical Implications. Ann. Intern. Med. 135, 279–295 (2001)Google Scholar
  7. 7.
    Wei, S.H., Parker, I., Miller, M.J., Cahalan, M.D.: A Stochastic View of Lymphocyte Motility and Trafficking Within the Lymph Node. Immunol. Rev. 195, 136–159 (2003)CrossRefGoogle Scholar
  8. 8.
    Cenk, S., Mempel, T.R., Mazo, I.B., Von Andrian, U.H.: Intravital Microscopy: Visualizing Immunity in Context. Immunity 21, 315–329 (2004)Google Scholar
  9. 9.
    Halin, C., Mora, J.R., Sumen, C., Von Andrian, U.H.: In Vivo Imaging of Lymphocyte Trafficking. Annu. Rev. Cell Dev. Biol. 21, 581–603 (2005)CrossRefGoogle Scholar
  10. 10.
    Bajénoff, M., Egen, J.G., Koo, L.Y., Laugier, J.P., Brau, F., Glaichenhaus, N., Germain, R.N.: Stromal Cells Networks Regulate Entry, Migration, and Territoriality in Lymph Nodes. Immunity 25, 1–13 (2006)CrossRefGoogle Scholar
  11. 11.
    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)CrossRefGoogle Scholar
  12. 12.
    Miller, M.J., Wei, S.H., Cahalan, M.D., Parker, I.: Autonomous T Cell Trafficking Examined In Vivo with Intravital Two-Photon Microscopy. PNAS 100, 2604–2609 (2003)CrossRefGoogle Scholar
  13. 13.
    Mempel, T., Henrickson, S.E., Von Andrian, U.H.: T-Cell Priming by Dendritic Cells in Lymph Nodes Occurs in Three Distinct Phases. Nature 427, 154–159 (2004)CrossRefGoogle Scholar
  14. 14.
    Okada, T., Miller, M.J., Parker, I., Matthew, F., Krummel, M.F., Neighbors, M., Hartley, S., O’Garra, A., Cahalan, M.D., Cyster, J.G.: Antigen-Engaged B Cells Undergo Chemotaxis toward the T Zone and Form Motile Conjugates with Helper T Cells. PLoS Biology 3(6), 1047–1061 (2005)CrossRefGoogle Scholar
  15. 15.
    Ma, B., Jablonska, J., Lindenmaier, W., Dittmar, K.: Immunohistochemical Study of the Reticular and Vascular Network of Mouse Lymph Node Using Vibratome Sections. Acta Histochem. 109, 15–28 (2007)CrossRefGoogle Scholar
  16. 16.
    Seiden, P.E., Celada, F.: A Model for Simulating Cognate Recognition and Response in the Immune System. J. Theor. Biology 158(3), 329–357 (1992)CrossRefGoogle Scholar
  17. 17.
    Efroni, S., Harel, D., Cohen, I.R.: Toward Rigorous Comprehension of Biological Complexity: Modeling, Execution, and Visualization of Thymic T-Cell Maturation. Gen. Res. 13, 2485–2497 (2003)CrossRefGoogle Scholar
  18. 18.
    Beltman, J.B., Marée, A., Lynch, N.L., Miller, M.J., De Boer, R.J.: Lymph Node Topology Dictates T Cell Migration Behavior. J. Exp. Med. 204(4), 771–780 (2007)CrossRefGoogle Scholar
  19. 19.
    Beltman, J.B., Marée, A., De Boer, R.J.: Spatial Modelling of Brief and Long Interactions between T Cells and Dendritic Cells. Imm. Cell Biol. (in press)Google Scholar
  20. 20.
    Stekel, D.J.: The Simulation of Density-Dependent Effects in the Recirculation of T Lymphocytes. Scand. J. Immunol. 47, 426–439 (1998)CrossRefGoogle Scholar
  21. 21.
    Stekel, D.J., Parker, C.E., Nowak, M.A.: A model of Lymphocyte Recirculation. Immunol. Today 18, 216–221 (1997)CrossRefGoogle Scholar
  22. 22.
    Beauchemin, C., Forrest, S., Koster, F.T.: Modeling Influenza Viral Dynamics in Tissue. In: Bersini, H., Carneiro, J. (eds.) ICARIS 2006. LNCS, vol. 4163, pp. 23–36. Springer, Heidelberg (2006)CrossRefGoogle Scholar
  23. 23.
    Murray, J.: Mathematical Biology. Springer, Heidelberg (1998)Google Scholar
  24. 24.
    Kallenberg, O.: Foundations of Modern Probability. Springer, Heidelberg (2002)MATHGoogle Scholar
  25. 25.
    Blaschke, V., Micheel, B., Pabst, R., Westermann, J.: Lymphocyte Traffic Through Lymph Nodes and Peyer’s Patches of the Rat: B- and T-Cell-Specific Migration Patterns Within the Tissue, and Their Dependence on Splenic Tissue. Cell Tissue Res. 282, 377–386 (1995)CrossRefGoogle Scholar
  26. 26.
    Uematsu, T., Sano, M., Homma, K.: In Vitro High-Resolution Helical CT of Small Axillary Lymph Nodes in Patients with Breast Cancer: Correlation of CT and Histology. Am. J. Roentgenol. 176, 1069–1074 (2001)Google Scholar
  27. 27.
    Westermann, J., Puskas, Z., Pabst, R.: Blood Transit and Recirculation Kinetics of Lymphocyte Subsets in Normal Rats. Scand. J. Immunol. 28, 203–210 (1988)CrossRefGoogle Scholar
  28. 28.
    Migration of So-Called Naive and Memory T Lymphocytes from Blood to Lymph in the Rat. J. Immunol. 152, 1744–1750 (1994)Google Scholar
  29. 29.
    Schwab, S., Pereira, J., Matloubian, M., Xu, Y., Huang, Y., Cyster, J.: Lymphocyte Sequestration Through S1P Lyase Inhibition and Disruption of S1P Gradients. Science 309, 1735–1739 (2005)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2007

Authors and Affiliations

  • Johannes Textor
    • 1
  • Jürgen Westermann
    • 2
  1. 1.Institut für Theoretische Informatik 
  2. 2.Institut für Anatomie, Universität zu Lübeck, 23538 LübeckGermany

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