Lung airway-surveilling CXCR3(hi) memory CD8(+) T cells are critical for protection against influenza A virus

Immunity. 2013 Nov 14;39(5):939-48. doi: 10.1016/j.immuni.2013.09.013.

Abstract

Inducing memory CD8(+) T cells specific for conserved antigens from influenza A virus (IAV) is a potential strategy for broadly protective vaccines. Here we show that memory CD8(+) T cells in the airways played an important role in early control of IAV. Expression of the chemokine receptor CXCR3 was critical for memory CD8(+) T cells to populate the airways during the steady state and vaccination approaches were designed to favor the establishment of memory CD8(+) T cells in the airways. Specifically, we found that interleukin-12 (IL-12) signaling shortly after immunization limited CXCR3 expression on memory CD8(+) T cells. Neutralization of IL-12 or adjuvants that did not induce high amounts of IL-12 enhanced CXCR3 expression, sustained airway localization of memory CD8(+) T cells, and resulted in superior protection against IAV.

Publication types

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

MeSH terms

  • Adoptive Transfer
  • Animals
  • Bronchoalveolar Lavage Fluid / immunology
  • CD8-Positive T-Lymphocytes / chemistry
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / transplantation
  • Chemotaxis, Leukocyte
  • Dendritic Cells / immunology
  • Immunization, Secondary
  • Immunologic Memory*
  • Influenza A virus / immunology
  • Influenza A virus / pathogenicity*
  • Influenza Vaccines / immunology*
  • Interleukin-12 / antagonists & inhibitors
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / immunology
  • Lung / immunology*
  • Lymph Nodes / immunology
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control*
  • Orthomyxoviridae Infections / virology
  • Receptor, Interferon alpha-beta / deficiency
  • Receptors, CXCR3 / biosynthesis
  • Receptors, CXCR3 / deficiency
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / physiology*
  • Respiratory System / immunology
  • STAT4 Transcription Factor / physiology
  • T-Lymphocyte Subsets / chemistry
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / transplantation
  • Vaccination

Substances

  • Cxcr3 protein, mouse
  • Ifnar1 protein, mouse
  • Influenza Vaccines
  • Receptors, CXCR3
  • STAT4 Transcription Factor
  • Stat4 protein, mouse
  • Receptor, Interferon alpha-beta
  • Interleukin-12