Alveolar epithelial cell chemokine expression triggered by antigen-specific cytolytic CD8+ T cell recognition
| Autor: | Carolina Soguero, Young S. Hahn, Angela N. Liu, Min Q. Zhao, Mark H. Stoler, Richard I. Enelow, Beiyang Wei |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Adoptive cell transfer
T cell Chemokine CXCL2 Receptors Antigen T-Cell Mice Transgenic CD8-Positive T-Lymphocytes Biology Lung injury Lymphocyte Activation Receptors Tumor Necrosis Factor Cell Line Alveolar cells Mice Interleukin 21 medicine Animals Cytotoxic T cell RNA Messenger Antigens Antigen-presenting cell Chemokine CCL2 In Situ Hybridization Inflammation Histocytochemistry Tumor Necrosis Factor-alpha Metalloendopeptidases Epithelial Cells General Medicine respiratory system Pulmonary Alveoli medicine.anatomical_structure Gene Expression Regulation Immunology Commentary Chemokines CD8 |
| Zdroj: | Journal of Clinical Investigation. 106:R49-R58 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci9786 |
| Popis: | CD8(+) T lymphocyte responses are a critical arm of the immune response to respiratory virus infection and may play a role in the pathogenesis of interstitial lung disease. We have shown that CD8(+) T cells induce significant lung injury in the absence of virus infection by adoptive transfer into mice with alveolar expression of a viral transgene. The injury is characterized by the parenchymal infiltration of host cells, primarily macrophages, which correlates with physiologic deficits in transgenic animals. CD8(+) T cell-mediated lung injury can occur in the absence of perforin and Fas expression as long as TNF-alpha is available. Here, we show that the effect of TNF-alpha expressed by CD8(+) T cells is mediated not exclusively by cytotoxicity, but also through the activation of alveolar target cells and their expression of inflammatory mediators. CD8(+) T cell recognition of alveolar cells in vitro triggered monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) expression in the targets, which was mediated by TNF-alpha. Antigen-dependent alveolar MCP-1 expression was observed in vivo as early as 3 hours after CD8(+) T cell transfer and depended upon TNF-R1 expression in transgenic recipients. MCP-1 neutralization significantly reduced parenchymal infiltration after T cell transfer. We conclude that alveolar epithelial cells actively participate in the inflammation and lung injury associated with CD8(+) T cell recognition of alveolar antigens. |
| Databáze: | OpenAIRE |
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