Alveolar epithelial cell chemokine expression triggered by antigen-specific cytolytic CD8(+) T cell recognition

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 inte rstitial lung disease. We have shown that CD8(+) T cells induce significant lung injury in the absence of virus infection by adoptive transfer into mi ce with alveolar expression of a viral transgene. The injury is characteriz ed by the parenchymal infiltration of host cells, primarily macrophages, wh ich correlates with physiologic deficits in transgenic animals. CD8(+) T ce ll-mediated lung injury can occur in the absence of perforin and Fas expres sion as long as TNF-alpha is available. Here, we show that the effect of TN F-alpha expressed by CD8(+) T cells is mediated not exclusively by cytotoxi city, but also through the activation of alveolar target cells and their ex pression of inflammatory mediators. CD8(+) T cell recognition of alveolar c ells in vitro triggered monocyte chemoattractant protein-1 (MCP-1) and macr ophage inflammatory protein-2 (MIP-2) expression in the targets, which was mediated by TNF-alpha. Antigen-dependent alveolar MCP-1 expression was obse rved in vivo as early as 3 hours after CD8+ T cell transfer and depended up on TNF-R1 expression in transgenic recipients. MCP-1 neutralization signifi cantly 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 .