CD8⁺ T cells with an intraepithelial phenotype upregulate cytotoxic function upon influenza infection in human lung

J Clin Invest. 2011 Jun;121(6):2254-63. doi: 10.1172/JCI44675. Epub 2011 May 2.


The human lung T cell compartment contains many CD8⁺ T cells specific for respiratory viruses, suggesting that the lung is protected from recurring respiratory infections by a resident T cell pool. The entry site for respiratory viruses is the epithelium, in which a subset of lung CD8⁺ T cells expressing CD103 (αE integrin) resides. Here, we determined the specificity and function of CD103⁺CD8⁺ T cells in protecting human lung against viral infection. Mononuclear cells were isolated from human blood and lung resection samples. Variable numbers of CD103⁺CD8⁺ T cells were retrieved from the lung tissue. Interestingly, expression of CD103 was seen only in lung CD8⁺ T cells specific for influenza but not in those specific for EBV or CMV. CD103⁺ and influenza-reactive cells preferentially expressed NKG2A, an inhibitor of CD8⁺ T cell cytotoxic function. In contrast to CD103⁻CD8⁺ T cells, most CD103⁺CD8⁺ cells did not contain perforin or granzyme B. However, they could quickly upregulate these cytotoxic mediators when exposed to a type I IFN milieu or via contact with their specific antigen. This mechanism may provide a rapid and efficient response to influenza infection, without inducing cytotoxic damage to the delicate epithelial barrier.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD / analysis
  • Blood Cells / immunology
  • CD8-Positive T-Lymphocytes / chemistry
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cytotoxicity, Immunologic
  • Epithelium / immunology
  • Female
  • Gene Expression Regulation / immunology
  • Granzymes / biosynthesis
  • Granzymes / genetics
  • Herpesviridae / immunology
  • Humans
  • Immunophenotyping
  • Influenza A virus / immunology
  • Influenza, Human / immunology*
  • Integrin alpha Chains / analysis
  • Integrin alpha1beta1 / analysis
  • Lung / immunology*
  • Male
  • Middle Aged
  • NK Cell Lectin-Like Receptor Subfamily C / analysis
  • Perforin
  • Pore Forming Cytotoxic Proteins / biosynthesis
  • Pore Forming Cytotoxic Proteins / genetics
  • T-Cell Antigen Receptor Specificity
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Up-Regulation


  • Antigens, CD
  • Integrin alpha Chains
  • Integrin alpha1beta1
  • KLRC1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily C
  • PRF1 protein, human
  • Pore Forming Cytotoxic Proteins
  • alpha E integrins
  • Perforin
  • GZMB protein, human
  • Granzymes