Selective dependence on IL-7 for antigen-specific CD8 T cell responses during airway influenza infection

Sci Rep. 2022 Jan 7;12(1):135. doi: 10.1038/s41598-021-03936-y.

Abstract

Interleukin-7 (IL-7) is a cytokine known for its importance in T cell development and survival. How IL-7 shapes CD8 T cell responses during an acute viral infection is less understood. We had previously shown that IL-7 signaling deficient mice have reduced accumulation of influenza-specific CD8 T cells following influenza infection. We sought to determine whether IL-7 affects early CD8 T cell expansion in the mediastinal lymph node and effector function in the lungs. Using IL-7Rα signaling deficient mice, we show that IL-7 is required for a normal sized mediastinal lymph node and the early clonal expansion of influenza-specific CD8 T cells therein. We show that IL-7 plays a cell-intrinsic role in the accumulation of NP366-374 and PA224-233-specific CD8 T cells in the lymph node. We also found that IL-7 shapes terminal differentiation, degranulation and cytokine production to a greater extent in PA224-233-specific than NP366-374-specific CD8 T cells. We further demonstrate that IL-7 is induced in the lung tissue by viral infection and we characterize multiple cellular sources that contribute to IL-7 production. Our findings on IL-7 and its effects on lower respiratory diseases will be important for expanding the utility of therapeutics that are currently available.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Alphainfluenzavirus / immunology
  • Alphainfluenzavirus / pathogenicity
  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / virology
  • Disease Models, Animal
  • Female
  • Host-Pathogen Interactions
  • Humans
  • Interleukin-7 / genetics
  • Interleukin-7 / metabolism*
  • Interleukin-7 Receptor alpha Subunit / genetics
  • Interleukin-7 Receptor alpha Subunit / metabolism
  • Lung / immunology
  • Lung / metabolism*
  • Lung / virology
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism*
  • Lymph Nodes / virology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation
  • Orthomyxoviridae Infections / genetics
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / metabolism*
  • Orthomyxoviridae Infections / virology
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / metabolism
  • Signal Transduction

Substances

  • IL7 protein, human
  • Interleukin-7
  • Interleukin-7 Receptor alpha Subunit
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor