CXCR3 enables recruitment and site-specific bystander activation of memory CD8+ T cells

Nat Commun. 2019 Nov 1;10(1):4987. doi: 10.1038/s41467-019-12980-2.

Abstract

Bystander activation of memory T cells occurs in the absence of cognate antigen during infections that elicit strong systemic inflammatory responses, which subsequently affect host immune responses. Here we report that memory T cell bystander activation is not limited to induction by systemic inflammation. We initially observe potential T cell bystander activation in a cohort of human vaccine recipients. Using a mouse model system, we then find that memory CD8+ T cells are specifically recruited to sites with activated antigen-presenting cells (APCs) in a CXCR3-dependent manner. In addition, CXCR3 is also necessary for T cell clustering around APCs and T cell bystander activation, which temporospatially overlaps with the subsequent antigen-specific T cell response. Our data thus suggest that bystander activation is part of the initial localized immune response, and is mediated by a site-specific recruitment process of memory T cells.

Publication types

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

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Antigens / immunology
  • Bystander Effect / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Female
  • Humans
  • Immunization
  • Immunologic Memory / immunology*
  • Inflammation / immunology
  • Lymphocyte Activation / immunology*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / immunology*
  • Receptors, CXCR3 / metabolism

Substances

  • Antigens
  • Cxcr3 protein, mouse
  • Receptors, CXCR3