Article ; Online: ADAM17-mediated processing of TNF-α expressed by antiviral effector CD8+ T cells is required for severe T-cell-mediated lung injury.
PLoS ONE, Vol 8, Iss 11, p e
2013 Volume 79340
Abstract: Influenza infection in humans evokes a potent CD8(+) T-cell response, which is important for clearance of the virus but may also exacerbate pulmonary pathology. We have previously shown in mice that CD8(+) T-cell expression of TNF-α is required for ... ...
Abstract | Influenza infection in humans evokes a potent CD8(+) T-cell response, which is important for clearance of the virus but may also exacerbate pulmonary pathology. We have previously shown in mice that CD8(+) T-cell expression of TNF-α is required for severe and lethal lung injury following recognition of an influenza antigen expressed by alveolar epithelial cells. Since TNF-α is first expressed as a transmembrane protein that is then proteolytically processed to release a soluble form, we sought to characterize the role of TNF-α processing in CD8(+) T-cell-mediated injury. In this study we observed that inhibition of ADAM17-mediated processing of TNF-α by CD8(+) T cells significantly attenuated the diffuse alveolar damage that occurs after T-cell transfer, resulting in enhanced survival. This was due in part to diminished chemokine expression, as TNF-α processing was required for lung epithelial cell expression of CXCL2 and the subsequent inflammatory infiltration. We confirmed the importance of CXCL2 expression in acute lung injury by transferring influenza-specific CD8(+) T cells into transgenic mice lacking CXCR2. These mice exhibited reduced airway infiltration, attenuated lung injury, and enhanced survival. Theses studies describe a critical role for TNF-α processing by CD8(+) T cells in the initiation and severity of acute lung injury, which may have important implications for limiting immunopathology during influenza infection and other human infectious or inflammatory diseases. |
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Keywords | Medicine ; R ; Science ; Q |
Subject code | 610 |
Language | English |
Publishing date | 2013-01-01T00:00:00Z |
Publisher | Public Library of Science (PLoS) |
Document type | Article ; Online |
Database | BASE - Bielefeld Academic Search Engine (life sciences selection) |
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