T RM integrins CD103 and CD49a differentially support adherence and motility after resolution of influenza virus infection

Proc Natl Acad Sci U S A. 2020 Jun 2;117(22):12306-12314. doi: 10.1073/pnas.1915681117. Epub 2020 May 21.

Abstract

Tissue-resident memory CD8 T (TRM) cells are a unique immune memory subset that develops and remains in peripheral tissues at the site of infection, providing future host resistance upon reexposure to that pathogen. In the pulmonary system, TRM are identified through S1P antagonist CD69 and expression of integrins CD103/β7 and CD49a/CD29(β1). Contrary to the established role of CD69 on CD8 T cells, the functions of CD103 and CD49a on this population are not well defined. This study examines the expression patterns and functions of CD103 and CD49a with a specific focus on their impact on T cell motility during influenza virus infection. We show that the TRM cell surface phenotype develops by 2 wk postinfection, with the majority of the population expressing CD49a and a subset that is also positive for CD103. Despite a previously established role in retaining TRM in peripheral tissues, CD49a facilitates locomotion of virus-specific CD8 T cells, both in vitro and in vivo. These results demonstrate that CD49a may contribute to local surveillance mechanisms of the TRM population.

Keywords: T cell; influenza; integrin; memory.

Publication types

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

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Adhesion
  • Cell Movement
  • Humans
  • Immunologic Memory
  • Influenza A Virus, H3N2 Subtype / genetics
  • Influenza A Virus, H3N2 Subtype / physiology*
  • Influenza, Human / genetics
  • Influenza, Human / immunology*
  • Influenza, Human / physiopathology
  • Influenza, Human / virology
  • Integrin alpha Chains / genetics
  • Integrin alpha Chains / immunology*
  • Integrin alpha1 / genetics
  • Integrin alpha1 / metabolism*
  • Mice, Inbred C57BL

Substances

  • Antigens, CD
  • Integrin alpha Chains
  • Integrin alpha1
  • alpha E integrins