Journal
JOURNAL OF IMMUNOLOGY
Volume 182, Issue 1, Pages 657-665Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.182.1.657
Keywords
-
Categories
Funding
- National Institutes of Health [HL62410, ES01 1810, HL89766]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [K08HL089766, R01HL062410] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [P01ES011810] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Hypersensitivity pneumonitis is an environmental lung disease characterized by a diffuse mononuclear cell infiltrate in the lung that can progress to pulmonary fibrosis with chronic exposure to an inhaled Ag. Using a well-established murine model of hypersensitivity pneumonitis, we repeatedly exposed C57BL/6 mice to Saccharopolyspora rectivirgula to investigate whether T cells are required for lung fibrosis. In the absence of alpha beta T cells, TCR beta(-/-) mice exposed to S. rectivirgula for 4 wk had markedly decreased mononuclear infiltrates and collagen deposition in the lung compared with wild-type C57BL/6 mice. In contrast to CD8(+) T cells, adoptive transfer of CD4(+) T cells reconstituted the S. rectivirgula-induced inflammatory and fibrotic response, suggesting that the CD4(+) T cell represents the critical alpha beta T cell subset. Cytokine analysis of lung homogenates at various time points after S. rectivirgula exposure failed to identify a predominant Th1 or Th2 phenotype. Conversely, IL-17 was found in the lung at increasing concentrations with continued exposure to S. rectivirgula. Intracellular cytokine staining revealed that 14% of CD4(+) T cells from the lung of mice treated with S. rectivirgula expressed IL-17A. In the absence of IL-17 receptor signaling, Il17ra(-/-) mice had significantly decreased lung inflammation and fibrosis compared with wild-type C57BL/6 mice. These data are the first to demonstrate an important role for Th17-polarized CD4(+) T lymphocytes in the immune response directed against S. rectivirgula in this murine model of hypersensitivity pneumonitis and pulmonary fibrosis. The Journal of Immunology, 2009,182: 657-665.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available