T cell and chemokine receptors differentially control CD8 T cell motility behavior in the infected airways immediately before and after virus clearance in a primary infection

PLoS One. 2020 Aug 20;15(8):e0227157. doi: 10.1371/journal.pone.0227157. eCollection 2020.

Abstract

In mice, experimental influenza virus infection stimulates CD8 T cell infiltration of the airways. Virus is cleared by day 9, and between days 8 and 9 there is an abrupt change in CD8 T cell motility behavior transitioning from low velocity and high confinement on day 8, to high velocity with continued high confinement on day 9. We hypothesized that loss of virus and/or antigen signals in the context of high chemokine levels drives the T cells into a rapid surveillance mode. Virus infection induces chemokine production, which may change when the virus is cleared. We therefore sought to examine this period of rapid changes to the T cell environment in the tissue and seek evidence on the roles of peptide-MHC and chemokine receptor interactions. Experiments were performed to block G protein coupled receptor (GPCR) signaling with Pertussis toxin (Ptx). Ptx treatment generally reduced cell velocities and mildly increased confinement suggesting chemokine mediated arrest (velocity <2 μm/min) (Friedman RS, 2005), except on day 8 when velocity increased and confinement was relieved. Blocking specific peptide-MHC with monoclonal antibody unexpectedly decreased velocities on days 7 through 9, suggesting TCR/peptide-MHC interactions promote cell mobility in the tissue. Together, these results suggest the T cells are engaged with antigen bearing and chemokine producing cells that affect motility in ways that vary with the day after infection. The increase in velocities on day 9 were reversed by addition of specific peptide, consistent with the idea that antigen signals become limiting on day 9 compared to earlier time points. Thus, antigen and chemokine signals act to alternately promote and restrict CD8 T cell motility until the point of virus clearance, suggesting the switch in motility behavior on day 9 may be due to a combination of limiting antigen in the presence of high chemokine signals as the virus is cleared.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / physiology
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Chemokines / immunology
  • Influenza A virus / immunology*
  • Influenza A virus / pathogenicity
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Orthomyxoviridae
  • Orthomyxoviridae Infections / immunology
  • Pertussis Toxin / metabolism
  • Pertussis Toxin / pharmacology
  • Receptors, Chemokine
  • Receptors, G-Protein-Coupled / metabolism

Substances

  • Chemokines
  • Receptors, Chemokine
  • Receptors, G-Protein-Coupled
  • Pertussis Toxin