Inflammatory monocytes contribute to the persistence of CXCR3hi CX3CR1lo circulating and lung-resident memory CD8+ T cells following respiratory virus infection

Immunol Cell Biol. 2018 Apr;96(4):370-378. doi: 10.1111/imcb.12006. Epub 2018 Jan 30.

Abstract

Phenotypically diverse memory CD8+ T cells are present in the lungs that either re-circulate or reside within the tissue. Understanding the key cellular interactions that regulate the generation and then persistence of these different subsets is of great interest. Recently, DNGR-1+ dendritic cell (DC) mediated priming was reported to control the generation of lung-resident but not circulating memory cells following respiratory viral infection. Here, we report an important role for Ly6C+ inflammatory monocytes (IMs) in contributing to the persistence of memory CD8+ T cells but not their generation. Effector CD8+ T cells expanded and contracted normally in the absence of IMs, but the memory compartment declined significantly over time. Quite unexpectedly, this defect was confined to tissue resident and circulating CXCR3hi CX3CR1lo memory cells but not CXCR3hi CX3CR1int and CXCR3lo CX3CR1hi subsets. Thus, two developmentally distinct innate cells orchestrate the generation and persistence of memory T cell subsets following a respiratory virus infection. See also: News and Commentary by Lafouresse & Groom.

Keywords: CD8+ T cells; lung; monocytes; resident memory T cells; vaccinia.

Publication types

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

MeSH terms

  • Administration, Intranasal
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CX3C Chemokine Receptor 1 / metabolism*
  • Cell Proliferation
  • Female
  • HeLa Cells
  • Humans
  • Immunity, Innate
  • Immunologic Memory*
  • Inflammation / pathology*
  • Lung / immunology*
  • Lung / pathology
  • Lung / virology
  • Mice, Inbred C57BL
  • Monocytes / pathology*
  • Receptors, CCR2 / deficiency
  • Receptors, CCR2 / metabolism
  • Receptors, CXCR3 / metabolism*
  • Respiratory Tract Infections / immunology
  • Respiratory Tract Infections / virology*
  • T-Lymphocyte Subsets / immunology
  • Vaccinia virus / physiology

Substances

  • CX3C Chemokine Receptor 1
  • Ccr2 protein, mouse
  • Receptors, CCR2
  • Receptors, CXCR3