Requirement for tumor necrosis factor-receptor 2 in alveolar chemokine expression depends upon the form of the ligand.
Respiratory virus infection evokes a potent T-cell response that may result in a considerable insult to the structural and functional integrity of the gas exchange units of the lung. Alveolar antigen recognition by CD8+ T lymphocytes results in significant injury that is critically dependent upon tumor necrosis factor (TNF)-alpha expressed by the CD8+ T cells and is largely dependent upon TNF-receptor 1 expression on the alveolar epithelial target cells. TNF-receptor 2 (TNF-R2)-deficient mice were used to demonstrate that CD8+ T-cell-mediated lung injury associated with clearance of experimental influenza requires TNF-R2 for full expression of immunopathology. In vitro analysis indicates that alveolar cell expression of TNF-R2 is critical in the induction of epithelial monocyte chemoattractant protein (MCP)-1 expression specifically in response to soluble TNF-alpha, suggesting an important role for this receptor in bystander lung injury. However, TNF-R2 was dispensable for induction of alveolar MCP-1 expression in response to transmembrane TNF-alpha expressed by antigen-specific CD8+ T cells, and the effects of the two receptors seem to be additive. Because TNF-R2 may be rapidly shed as part of feedback inhibition of bystander inflammation, this suggests a mechanism by which immunopathology in respiratory virus infection may be regulated and by which T-cell receptor-dependent TNF-alpha activity might bypass such negative regulation for contact-dependent antiviral activities.
Liu
Jun
J
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Zhao
Min Q
MQ
Xu
Lumei
L
Ramana
C V
CV
Declercq
Wim
W
Vandenabeele
Peter
P
Enelow
Richard I
RI
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000821:virology; D018932:Chemokine CCL2 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D008024:Ligands; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D008171:Lung Diseases / Q000276:immunology* / Q000473:pathology / Q000821:virology; D051379:Mice; D008817:Mice, Mutant Strains; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000276:immunology*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology*
D018932:Chemokine CCL2; D018925:Chemokines; D008024:Ligands; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha