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CD8+ T cells with an intraepithelial phenotype upregulate cytotoxic function upon influenza infection in human lung
Berber Piet, … , René A.W. van Lier, René E. Jonkers
Berber Piet, … , René A.W. van Lier, René E. Jonkers
Published May 2, 2011
Citation Information: J Clin Invest. 2011;121(6):2254-2263. https://doi.org/10.1172/JCI44675.
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Research Article Immunology

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

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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.

Authors

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

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Figure 5

CD8+CD103+ lung T cells have a low cytotoxic potential and a high expression of the inhibitory NK cell receptor complex CD94/NKG2A.

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CD8+CD103+ lung T cells have a low cytotoxic potential and a high expres...
(A) FACS plots show the expression of perforin, granzyme B, CD94, and NKG2A plotted against CD103 expression. Plots show only CD3+CD8+ lung T cells within the lymphocyte gate and are representative of 22–30 patients. Numbers indicate the percentages of CD3+CD8+ cells that are located within each quadrant. (B) Most lung CD8+ T cells express CD94 and NKG2A to the same extent, which is suggestive of dimerization (left). Numbers indicate the percentages of CD3+CD8+ cells that are located within each quadrant. Moreover, lung CD8+ T cells hardly express the activating isoform NKG2C, and there is no difference in NKG2C expression between CD103+ and CD103– T cells (right, n = 5). (C) The percentage of CD103+CD8+ and CD103–CD8+ lung T cells containing perforin or granzyme B (n = 22). (D) The percentage of CD103+CD8+ and CD103–CD8+ lung T cells expressing CD94 (n = 27) and NKG2A (n = 30). All expression data were collected with flow cytometry; all FACS plots show only lung CD3+CD8+ lymphocytes within the lymphocyte gate. ***P < 0.0001.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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