Tuning of antigen sensitivity by T cell receptor-dependent negative feedback controls T cell effector function in inflamed tissues

Immunity. 2014 Feb 20;40(2):235-247. doi: 10.1016/j.immuni.2013.11.017. Epub 2014 Jan 16.


Activated T cells must mediate effector responses sufficiently to clear pathogens while avoiding excessive tissue damage. Here we have combined dynamic intravital microscopy with ex vivo assessments of T cell cytokine responses to generate a detailed spatiotemporal picture of CD4(+) T cell effector regulation in the skin. In response to antigen, effector T cells arrested transiently on antigen-presenting cells, briefly producing cytokine and then resuming migration. Antigen recognition led to upregulation of the programmed death-1 (PD-1) glycoprotein by T cells and blocking its canonical ligand, programmed death-ligand 1 (PD-L1), lengthened the duration of migration arrest and cytokine production, showing that PD-1 interaction with PD-L1 is a major negative feedback regulator of antigen responsiveness. We speculate that the immune system employs T cell recruitment, transient activation, and rapid desensitization to allow the T cell response to rapidly adjust to changes in antigen presentation and minimize collateral injury to the host.

Publication types

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

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigens / immunology
  • Cell Movement
  • Feedback, Physiological*
  • Flow Cytometry
  • Inflammation / immunology*
  • Inflammation / physiopathology
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological*
  • Receptors, Antigen, T-Cell / immunology*
  • Skin / immunology
  • T-Lymphocytes / immunology*


  • Antigens
  • Receptors, Antigen, T-Cell