Generalized Lévy walks and the role of chemokines in migration of effector CD8+ T cells

Nature. 2012 Jun 28;486(7404):545-8. doi: 10.1038/nature11098.

Abstract

Chemokines have a central role in regulating processes essential to the immune function of T cells, such as their migration within lymphoid tissues and targeting of pathogens in sites of inflammation. Here we track T cells using multi-photon microscopy to demonstrate that the chemokine CXCL10 enhances the ability of CD8+ T cells to control the pathogen Toxoplasma gondii in the brains of chronically infected mice. This chemokine boosts T-cell function in two different ways: it maintains the effector T-cell population in the brain and speeds up the average migration speed without changing the nature of the walk statistics. Notably, these statistics are not Brownian; rather, CD8+ T-cell motility in the brain is well described by a generalized Lévy walk. According to our model, this unexpected feature enables T cells to find rare targets with more than an order of magnitude more efficiency than Brownian random walkers. Thus, CD8+ T-cell behaviour is similar to Lévy strategies reported in organisms ranging from mussels to marine predators and monkeys, and CXCL10 aids T cells in shortening the average time taken to find rare targets.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Brain / immunology
  • Brain / microbiology
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Movement*
  • Chemokine CXCL10 / antagonists & inhibitors
  • Chemokine CXCL10 / genetics
  • Chemokine CXCL10 / immunology*
  • Female
  • Ligands
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Models, Immunological
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / metabolism
  • Time Factors
  • Toxoplasma / growth & development
  • Toxoplasma / immunology

Substances

  • Chemokine CXCL10
  • Cxcl10 protein, mouse
  • Ligands
  • Receptors, CXCR3