IL-15 enhances CCR5-mediated migration of memory CD8+ T cells by upregulating CCR5 expression in the absence of TCR stimulation

Cell Rep. 2021 Jul 27;36(4):109438. doi: 10.1016/j.celrep.2021.109438.

Abstract

During microbial infection, bystander CD8+ T cells that are not specific to infecting pathogens can be activated by interleukin (IL)-15. However, the tissue-homing properties of bystander-activated CD8+ T cells have not been elucidated. Here, we examine the effects of IL-15 on the expression of chemokine receptors on CD8+ T cells and their migration. IL-15 upregulates CCR5 in memory CD8+ T cells in the absence of T cell receptor (TCR) stimulation and enhances CCR5-dependent migration. IL-15-induced CCR5 upregulation is abrogated by TCR stimulation, indicating that CCR5 is upregulated in bystander-activated CD8+ T cells. Moreover, CCR5 signals increase proliferation and cytotoxic protein expression in IL-15-treated memory CD8+ T cells, although the increase has a small extent. CCR5 upregulation in bystander-activated CD8+ T cells is associated with severe liver injury in patients with acute hepatitis A. Altogether, the results indicate that CCR5 upregulation by IL-15 mediates the migration of bystander-activated CD8+ T cells.

Keywords: CCR5; IL-15; bystander-activated CD8(+) T cells; migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Animals
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Death / genetics
  • Cell Movement*
  • Cell Proliferation / genetics
  • Female
  • Hepatitis A / complications
  • Hepatitis A / genetics
  • Hepatitis A / immunology
  • Humans
  • Immunologic Memory*
  • Inflammation / complications
  • Inflammation / immunology
  • Inflammation / pathology
  • Interleukin-15 / metabolism*
  • MAP Kinase Signaling System
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, CCR5 / genetics*
  • Receptors, CCR5 / metabolism
  • Receptors, CCR7 / metabolism
  • Up-Regulation / genetics
  • Young Adult

Substances

  • CCR7 protein, human
  • Interleukin-15
  • Receptors, Antigen, T-Cell
  • Receptors, CCR5
  • Receptors, CCR7