Lymph node topology dictates T cell migration behavior
Open Access
- 26 March 2007
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 204 (4), 771-780
- https://doi.org/10.1084/jem.20061278
Abstract
Adaptive immunity is initiated by T cell recognition of foreign peptides presented on dendritic cells (DCs) by major histocompatibility molecules. These interactions take place in secondary lymphoid tissues, such as lymph nodes (LNs) and spleen, and hence the anatomical structure of these tissues plays a crucial role in the development of immune responses. Two-photon microscopy (2PM) imaging in LNs suggests that T cells walk in a consistent direction for several minutes, pause briefly with a regular period, and then take off in a new, random direction. Here, we construct a spatially explicit model of T cell and DC migration in LNs and show that all dynamical properties of T cells could be a consequence of the densely packed LN environment. By means of 2PM experiments, we confirm that the large velocity fluctuations of T cells are indeed environmentally determined rather than resulting from an intrinsic motility program. Our simulations further predict that T cells self-organize into microscopically small, highly dynamic streams. We present experimental evidence for the presence of such turbulent streams in LNs. Finally, the model allows us to estimate the scanning rates of DCs (2,000 different T cells per hour) and T cells (100 different DCs per hour).Keywords
This publication has 38 references indexed in Scilit:
- Stromal Cell Networks Regulate Lymphocyte Entry, Migration, and Territoriality in Lymph NodesImmunity, 2006
- Sphingosine 1-phosphate type 1 receptor agonism inhibits transendothelial migration of medullary T cells to lymphatic sinusesNature Immunology, 2005
- Directed Migration of Positively Selected Thymocytes Visualized in Real TimePLoS Biology, 2005
- A novel reticular stromal structure in lymph node cortex: an immuno-platform for interactions among dendritic cells, T cells and B cellsInternational Immunology, 2004
- T-cell priming by dendritic cells in lymph nodes occurs in three distinct phasesNature, 2004
- The Strategy of T Cell Antigen-presenting Cell Encounter in Antigen-draining Lymph Nodes Revealed by Imaging of Initial T Cell ActivationThe Journal of Experimental Medicine, 2003
- Two-Photon Imaging of Lymphocyte Motility and Antigen Response in Intact Lymph NodeScience, 2002
- Estimating the Precursor Frequency of Naive Antigen-specific CD8 T CellsThe Journal of Experimental Medicine, 2002
- Evolving Mechanisms of Morphogenesis: on the Interplay between Differential Adhesion and Cell DifferentiationJournal of Theoretical Biology, 2000
- Can Surface Adhesion Drive Cell-rearrangement? Part I: Biological Cell-sortingJournal of Theoretical Biology, 1993