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Dynamics of CD8+ T cell priming by dendritic cells in intact lymph nodes

Abstract

The cellular dynamics underlying activation of CD8+ T cells by dendritic cells (DCs) in the lymph node are not known. Here we have tracked the behavior of T cells and DCs by subjecting intact lymph nodes to real-time two-photon microscopy. We show that DCs scan at least 500 different T cells per hour in the absence of antigen. Antigen-bearing DCs are highly efficient in recruiting peptide-specific T cells and can engage more than ten T cells simultaneously. The duration of these interactions is of the order of hours, not minutes. The overall avidity of the interaction influences the probability that T cells will be stably captured by DCs, providing a possible basis for T cell competition. Taken together, our results identify the cellular behaviors that promote an efficient CD8+ T cell response in the lymph node.

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Figure 1: Motility of T cells and DCs in the lymph node.
Figure 2: T cell migration promotes very efficient scanning of the T cell repertoire by an individual DC.
Figure 3: Changes in CD8+ T cell behavior on antigen recognition.
Figure 4: Priming of CD8+ T cells by DCs occurs as long-lasting interactions.
Figure 5: Impact of DC density on T cell–DC contacts.
Figure 6: Low-avidity interactions result in inefficient recruitment of peptide-specific T cells by antigen-bearing DCs.

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References

  1. Ingulli, E., Mondino, A., Khoruts, A. & Jenkins, M.K. In vivo detection of dendritic cell antigen presentation to CD4+ T cells. J. Exp. Med. 185, 2133–2141 (1997).

    Article  CAS  Google Scholar 

  2. Schaefer, B.C., Schaefer, M.L., Kappler, J.W., Marrack, P. & Kedl, R.M. Observation of antigen-dependent CD8+ T-cell/dendritic cell interactions in vivo. Cell Immunol. 214, 110–122 (2001).

    Article  CAS  Google Scholar 

  3. Norbury, C.C., Malide, D., Gibbs, J.S., Bennink, J.R. & Yewdell, J.W. Visualizing priming of virus-specific CD8+ T cells by infected dendritic cells in vivo. Nat. Immunol. 3, 265–271 (2002).

    Article  CAS  Google Scholar 

  4. 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  Google Scholar 

  5. Negulescu, P.A., Krasieva, T.B., Khan, A., Kerschbaum, H.H. & Cahalan, M.D. Polarity of T cell shape, motility, and sensitivity to antigen. Immunity 4, 421–430 (1996).

    Article  CAS  Google Scholar 

  6. Dustin, M.L., Bromley, S.K., Kan, Z., Peterson, D.A. & Unanue, E.R. Antigen receptor engagement delivers a stop signal to migrating T lymphocytes. Proc. Natl. Acad. Sci. USA 94, 3909–3913 (1997).

    Article  CAS  Google Scholar 

  7. Monks, C.R., Freiberg, B.A., Kupfer, H., Sciaky, N. & Kupfer, A. Three-dimensional segregation of supramolecular activation clusters in T cells. Nature 395, 82–86 (1998).

    Article  CAS  Google Scholar 

  8. Wulfing, C. & Davis, M.M. A receptor/cytoskeletal movement triggered by costimulation during T cell activation. Science 282, 2266–2269 (1998).

    Article  CAS  Google Scholar 

  9. Grakoui, A. et al. The immunological synapse: a molecular machine controlling T cell activation. Science 285, 221–227 (1999).

    Article  CAS  Google Scholar 

  10. Underhill, D.M., Bassetti, M., Rudensky, A. & Aderem, A. Dynamic interactions of macrophages with T cells during antigen presentation. J. Exp. Med. 190, 1909–1914 (1999).

    Article  CAS  Google Scholar 

  11. Gunzer, M. et al. Antigen presentation in extracellular matrix: interactions of T cells with dendritic cells are dynamic, short lived, and sequential. Immunity 13, 323–332 (2000).

    Article  CAS  Google Scholar 

  12. Bousso, P., Bhakta, N.R., Lewis, R.B. & Robey, E. Dynamics of thymocyte–stromal cell interactions visualized by two-photon microscopy. Science 296, 1876–1880 (2002).

    Article  CAS  Google Scholar 

  13. 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).

    Article  CAS  Google Scholar 

  14. 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  Google Scholar 

  15. Porgador, A. et al. Predominant role for directly transfected dendritic cells in antigen presentation to CD8+ T cells after gene gun immunization. J. Exp. Med. 188, 1075–1082 (1998).

    Article  CAS  Google Scholar 

  16. Cumberbatch, M., Dearman, R.J. & Kimber, I. Influence of ageing on Langerhans cell migration in mice: identification of a putative deficiency of epidermal interleukin-1β. Immunology 105, 466–477 (2002).

    Article  CAS  Google Scholar 

  17. Pircher, H., Burki, K., Lang, R., Hengartner, H. & Zinkernagel, R.M. Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen. Nature 342, 559–561 (1989).

    Article  CAS  Google Scholar 

  18. 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, 2506–2509 (2003).

    Google Scholar 

  19. Grufman, P., Wolpert, E.Z., Sandberg, J.K. & Karre, K. T cell competition for the antigen-presenting cell as a model for immunodominance in the cytotoxic T lymphocyte response against minor histocompatibility antigens. Eur. J. Immunol. 29, 2197–2204 (1999).

    Article  CAS  Google Scholar 

  20. Kedl, R.M. et al. T cells compete for access to antigen-bearing antigen-presenting cells. J. Exp. Med. 192, 1105–1113 (2000).

    Article  CAS  Google Scholar 

  21. Savage, P.A., Boniface, J.J. & Davis, M.M. A kinetic basis for T cell receptor repertoire selection during an immune response. Immunity 10, 485–492 (1999).

    Article  CAS  Google Scholar 

  22. Busch, D.H. & Pamer, E.G. T cell affinity maturation by selective expansion during infection. J. Exp. Med. 189, 701–710 (1999).

    Article  CAS  Google Scholar 

  23. Rees, W. et al. An inverse relationship between T cell receptor affinity and antigen dose during CD4+ T cell responses in vivo and in vitro. Proc. Natl. Acad. Sci. USA 96, 9781–9786 (1999).

    Article  CAS  Google Scholar 

  24. Kedl, R.M., Schaefer, B.C., Kappler, J.W. & Marrack, P. T cells down-modulate peptide-MHC complexes on APCs in vivo. Nat. Immunol. 3, 27–32 (2002).

    Article  CAS  Google Scholar 

  25. Shortman, K. & Liu, Y.J. Mouse and human dendritic cell subtypes. Nat. Rev. Immunol. 3, 151–161 (2002).

    Article  Google Scholar 

  26. Reichert, P., Reinhardt, R.L., Ingulli, E. & Jenkins, M.K. Cutting edge: in vivo identification of TCR redistribution and polarized IL-2 production by naive CD4+ T cells. J. Immunol. 166, 4278–4281 (2001).

    Article  CAS  Google Scholar 

  27. McGavern, D.B., Christen, U. & Oldstone, M.B. Molecular anatomy of antigen-specific CD8+ T cell engagement and synapse formation in vivo. Nat. Immunol. 3, 918–925 (2002).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank H. Aaron for assistance with microscopy, N. Bhakta for advice on velocity measurements and N. Fernandez, W. Sha, D. Raulet and the members of the Robey laboratory for comments on the manuscript. This work was supported by NIH grants AI32985 and AI42033. P.B. is supported by the Cancer Research Institute.

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Correspondence to Philippe Bousso.

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Bousso, P., Robey, E. Dynamics of CD8+ T cell priming by dendritic cells in intact lymph nodes. Nat Immunol 4, 579–585 (2003). https://doi.org/10.1038/ni928

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