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Mouse Models Reveal Role of T-Cytotoxic and T-Reg Cells in Immune Response to Influenza: Implications for Vaccine Design

1
New York State Department of Health, Wadsworth Center, Empire State Plaza, Albany, NY 12201, USA
2
School of Public Health, University at Albany, Rensselaer, NY 12144, USA
3
Albany College of Pharmacy and Health Sciences, Albany, NY 12208, USA
4
Burnett School of Biomedical Sciences, University of Central Florida Medical School, Orlando, FL 32816, USA
*
Author to whom correspondence should be addressed.
Viruses 2019, 11(1), 52; https://doi.org/10.3390/v11010052
Received: 14 November 2018 / Revised: 4 January 2019 / Accepted: 7 January 2019 / Published: 11 January 2019
(This article belongs to the Special Issue Animal Models for Viral Diseases)
Immunopathologic examination of the lungs of mouse models of experimental influenza virus infection provides new insights into the immune response in this disease. First, there is rapidly developing perivascular and peribronchial infiltration of the lung with T-cells. This is followed by invasion of T-cells into the bronchiolar epithelium, and separation of epithelial cells from each other and from the basement membrane leading to defoliation of the bronchial epithelium. The intraepithelial reaction may involve either CD8 or CD4 T-cytotoxic cells and is analogous to a viral exanthema of the skin, such as measles and smallpox, which occur when the immune response against these infections is activated and the infected cells are attacked by T-cytotoxic cells. Then there is formation of B-cell follicles adjacent to bronchi, i.e., induced bronchial associated lymphoid tissue (iBALT). iBALT reacts like the cortex of a lymph node and is a site for a local immune response not only to the original viral infection, but also related viral infections (heterologous immunity). Proliferation of Type II pneumocytes and/or terminal bronchial epithelial cells may extend into the adjacent lung leading to large zones filled with tumor-like epithelial cells. The effective killing of influenza virus infected epithelial cells by T-cytotoxic cells and induction of iBALT suggests that adding the induction of these components might greatly increase the efficacy of influenza vaccination. View Full-Text
Keywords: influenza; T-cell cytoxicity; viral exanthema; iBALT; epithelial proliferation; mouse models; influenza vaccination influenza; T-cell cytoxicity; viral exanthema; iBALT; epithelial proliferation; mouse models; influenza vaccination
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Sell, S.; McKinstry, K.K.; Strutt, T.M. Mouse Models Reveal Role of T-Cytotoxic and T-Reg Cells in Immune Response to Influenza: Implications for Vaccine Design. Viruses 2019, 11, 52.

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