PMID- 10995793 OWN - NLM STAT- MEDLINE DCOM- 20001012 LR - 20181113 IS - 0021-9738 (Print) IS - 1558-8238 (Electronic) IS - 0021-9738 (Linking) VI - 106 IP - 6 DP - 2000 Sep TI - Alveolar epithelial cell chemokine expression triggered by antigen-specific cytolytic CD8(+) T cell recognition. PG - R49-58 AB - 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. FAU - Zhao, M Q AU - Zhao MQ AD - Department of Medicine, The Beirne B. Carter Center for Immunology Research, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA. FAU - Stoler, M H AU - Stoler MH FAU - Liu, A N AU - Liu AN FAU - Wei, B AU - Wei B FAU - Soguero, C AU - Soguero C FAU - Hahn, Y S AU - Hahn YS FAU - Enelow, R I AU - Enelow RI LA - eng GR - R01 HL058660/HL/NHLBI NIH HHS/United States GR - R29 HL058660/HL/NHLBI NIH HHS/United States GR - HL58660/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 0 (Antigens) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CXCL2) RN - 0 (Chemokines) RN - 0 (Cxcl2 protein, mouse) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Antigen, T-Cell) RN - 0 (Receptors, Tumor Necrosis Factor) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 3.4.24.- (Metalloendopeptidases) SB - IM CIN - J Clin Invest. 2000 Sep;106(6):741-3. PMID: 10995783 MH - Animals MH - Antigens/*immunology/metabolism MH - CD8-Positive T-Lymphocytes/*immunology/metabolism MH - Cell Line MH - Chemokine CCL2/genetics/immunology/metabolism MH - Chemokine CXCL2 MH - Chemokines/genetics/immunology/*metabolism MH - Epithelial Cells/immunology/*metabolism/pathology MH - Gene Expression Regulation/drug effects MH - Histocytochemistry MH - In Situ Hybridization MH - Inflammation/immunology MH - Lymphocyte Activation MH - Metalloendopeptidases/antagonists & inhibitors MH - Mice MH - Mice, Transgenic MH - Pulmonary Alveoli/*immunology/*metabolism/pathology MH - RNA, Messenger/analysis MH - Receptors, Antigen, T-Cell/immunology MH - Receptors, Tumor Necrosis Factor/metabolism MH - Tumor Necrosis Factor-alpha/metabolism/pharmacology PMC - PMC381394 EDAT- 2000/09/21 11:00 MHDA- 2000/10/14 11:01 PMCR- 2000/09/15 CRDT- 2000/09/21 11:00 PHST- 2000/09/21 11:00 [pubmed] PHST- 2000/10/14 11:01 [medline] PHST- 2000/09/21 11:00 [entrez] PHST- 2000/09/15 00:00 [pmc-release] AID - 09786 [pii] AID - 10.1172/JCI9786 [doi] PST - ppublish SO - J Clin Invest. 2000 Sep;106(6):R49-58. doi: 10.1172/JCI9786.