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Am J Respir Cell Mol Biol. 2017 Jun 14. doi: 10.1165/rcmb.2016-0377OC. [Epub ahead of print]
Human CD8+ T Cells Damage Non-infected Epithelial Cells During Influenza Virus Infection In Vitro.
van de Sandt CE1, B?rcena M2, Koster AJ3, Kasper J4, Kirkpatrick CJ5, Scott DP6, de Vries RD7, Herold S8, Rimmelzwaan GF9, Kuiken T10, Short KR11,12,13.
Author information
Abstract
During severe influenza A virus (IAV) infections a large amount of damage to the pulmonary epithelium is the result of the anti-viral immune response. Specifically, whilst CD8+ T cells are important for killing IAV-infected cells, during a severe IAV infection they can damage uninfected epithelial cells. At present, the mechanisms by which this occurs are unclear. Here, we used a novel in vitro co-culture model of human NCl-H441 cells and CD8+ T cells in order to provide a new insight into how CD8+ T cells may affect uninfected epithelial cells during severe IAV infections. Using this model, we show that human IAV-specific CD8+ T cells produce soluble factors that reduce the barrier integrity of non-infected epithelial cells (referred to as 'bystander damage'). We show that this bystander damage is the result of a combination of TNFα and IFNγ. This bystander damage occurred in the absence of widespread epithelial cell death, and was instead associated with decreased expression of epithelial cell ion channels and pumps. Together, these data suggest that ameliorating the function of epithelial cell ion channels and pumps may help reduce immunopathology during severe IAV infections.
KEYWORDS:
CD8+ T cells; bystander damage; epithelial cells; influenza
PMID: 28613916 DOI: 10.1165/rcmb.2016-0377OC
Human CD8+ T Cells Damage Non-infected Epithelial Cells During Influenza Virus Infection In Vitro.
van de Sandt CE1, B?rcena M2, Koster AJ3, Kasper J4, Kirkpatrick CJ5, Scott DP6, de Vries RD7, Herold S8, Rimmelzwaan GF9, Kuiken T10, Short KR11,12,13.
Author information
Abstract
During severe influenza A virus (IAV) infections a large amount of damage to the pulmonary epithelium is the result of the anti-viral immune response. Specifically, whilst CD8+ T cells are important for killing IAV-infected cells, during a severe IAV infection they can damage uninfected epithelial cells. At present, the mechanisms by which this occurs are unclear. Here, we used a novel in vitro co-culture model of human NCl-H441 cells and CD8+ T cells in order to provide a new insight into how CD8+ T cells may affect uninfected epithelial cells during severe IAV infections. Using this model, we show that human IAV-specific CD8+ T cells produce soluble factors that reduce the barrier integrity of non-infected epithelial cells (referred to as 'bystander damage'). We show that this bystander damage is the result of a combination of TNFα and IFNγ. This bystander damage occurred in the absence of widespread epithelial cell death, and was instead associated with decreased expression of epithelial cell ion channels and pumps. Together, these data suggest that ameliorating the function of epithelial cell ion channels and pumps may help reduce immunopathology during severe IAV infections.
KEYWORDS:
CD8+ T cells; bystander damage; epithelial cells; influenza
PMID: 28613916 DOI: 10.1165/rcmb.2016-0377OC