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

Berber Piet*, Godelieve J. de Bree, Barbara S. Smids-Dierdorp, Chris M. van der Loos, Ester B. M. Remmerswaal, Jan H. von der Thusen, Jan M. W. van Haarst, Jan P. Eerenberg, Anja ten Brinke, Wim van der Bij, Wim Timens, Rene A. W. van Lier, Rene E. Jonkers

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

109 Citations (Scopus)

Abstract

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 CD 103 (alpha E 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 IIFN 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.

Original languageEnglish
Pages (from-to)2254-2263
Number of pages10
JournalThe Journal of Clinical Investigation
Volume121
Issue number6
DOIs
Publication statusPublished - Jun-2011

Keywords

  • OBSTRUCTIVE PULMONARY-DISEASE
  • VIRUS INFECTION
  • E-CADHERIN
  • ALPHA(E)BETA(7) INTEGRIN
  • RECEPTORS CD94/NKG2A
  • INHIBITORY RECEPTORS
  • RESPIRATORY VIRUSES
  • PERIPHERAL-TISSUES
  • EPITHELIAL-CELLS
  • CUTTING EDGE

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