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

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 2

Influenza-specific lung CD8+ T cells have an intraepithelial phenotype, expressing CD103, VLA-1, and NKG2A, whereas cells specific for nonrespiratory viruses lack the expression of these epithelial markers.

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Influenza-specific lung CD8+ T cells have an intraepithelial phenotype, ...
(A) FACS plots showing tetramer stainings on lung CD3+ cells after gating on live cells. Numbers indicate the percentages of CD3+ cells that are tetramer+. (B) Percentages of influenza-specific, EBV-specific, and CMV-specific lung CD8+ T cells expressing CD103, NKG2A, and VLA-1, as assessed by flow cytometry (n = 5–9 per tetramer). Bars represent the median. (C) Representative FACS plots for phenotype of lung and peripheral blood CD8+ T cells. FACS plots show the expression of CD103, NKG2A, and VLA-1 on total lung CD8+ T cells (left column), on FLU- and EBV-specific lung CD8+ T cells (second and third columns, respectively), on total peripheral blood CD8+ T cells (fourth column), and on FLU- and EBV-specific peripheral blood CD8+ T cells (fifth and sixth columns, respectively). Numbers in first and fourth columns indicate the percentages of CD3+CD8+ cells that are CD103+, NKG2A+, or VLA-1+. Numbers in second, third, fifth, and sixth columns indicate the percentages of tetramer+ cells that are CD103+, NKG2A+, or VLA-1+. Plots are representative of 5 to 9 patients per tetramer (lung) or 2 to 6 patients per tetramer (peripheral blood). FLU-specific cells could often not be detected in the blood with tetramer staining, although these patients did have FLU+ cells in the lung. CD8+ T cells were all identified as CD3+CD8+ cells within the lymphocyte gate.