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

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.