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- Title
CD8⁺ T cells with an intraepithelial phenotype upregulate cytotoxic function upon influenza infection in human lung.
- Authors
Piet, Berber; de Bree, Godelieve J.; Smids-Dierdorp, Barbara S.; van der Loos, Chris M.; Remmerswaal, Ester B. M.; von der Thüsen, Jan H.; van Haarst, Jan M. W.; Eerenberg, Jan P.; Brinke, Anja ten; Wim van der Bij; Wim Timens; van Lier, René A. W.; Jonkers, René E.; von der Thüsen, Jan H; ten Brinke, Anja; van der Bij, Wim; Timens, Wim; van Lier, René A W; Jonkers, René E
- 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 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.
- Subjects
T cells; CELL-mediated cytotoxicity; RESPIRATORY infections; LUNG diseases; EPITHELIUM; INFLUENZA A virus; INTEGRINS; LABORATORY mice; ANTIGEN analysis; PROTEINS; BIOCHEMISTRY; RESEARCH; LUNGS; RESEARCH methodology; PROTEOLYTIC enzymes; CELL receptors; MEDICAL cooperation; EVALUATION research; BLOOD cells; PHENOMENOLOGY; COMPARATIVE studies; INFLUENZA; IMMUNITY; IMMUNOPHENOTYPING; GENES; HERPESVIRUSES; CYTOTOXINS
- Publication
Journal of Clinical Investigation, 2011, Vol 121, Issue 6, p2254
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI44675