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Subtle CXCR3-Dependent Chemotaxis of CTLs within Infected Tissue Allows Efficient Target Localization.

Silvia Ariotti1, Joost B Beltman2, Rianne Borsje1

  • 1Division of Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands;

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|November 4, 2015
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Cytotoxic T lymphocytes (CTLs) use subtle, distance-dependent chemotaxis toward infected cells, mediated by CXCR3, to efficiently locate targets within peripheral tissues. This migration is crucial for rapid T cell accumulation at infection sites.

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Area of Science:

  • Immunology
  • Cell Biology
  • Virology

Background:

  • Effector T cells enter infected tissues, but their migration to specific infected cells is not fully understood.
  • The chemokine receptor CXCR3 is known to be important for T cell localization and controlling viral infections.

Purpose of the Study:

  • To investigate the migration strategies of cytotoxic T lymphocytes (CTLs) towards virus-infected cells within peripheral tissues.
  • To analyze the role of chemotaxis and CXCR3 in CTL localization to Herpes Simplex Virus-1 (HSV-1) infected cells in vivo.

Main Methods:

  • In vivo analysis of CTL migration within HSV-1-infected epidermis.
  • Computer simulations based on experimental migration data.
  • Long-term imaging of T cell-target interactions.

Main Results:

  • Activated T cells exhibit weak, distance-dependent chemotaxis towards clusters of infected cells.
  • This chemotactic behavior is confirmed to be mediated by the CXCR3 receptor and its ligands.
  • Computer simulations and long-term imaging reveal this chemotaxis is critical for efficient target localization and T cell accumulation.

Conclusions:

  • Chemotactic migration of effector T cells within peripheral tissues is a key factor in their rapid arrival at infection sites.
  • CXCR3-mediated chemotaxis plays a vital role in the efficiency of CTLs finding and accumulating at virus-infected cells.