Polarized Type 1 Cytokine Profile in Bronchoalveolar Lavage T Cells of Patients with Hypersensitivity Pneumonitis

Abstract

Hypersensitivity pneumonitis (HP) is characterized by an inflammatory lymphocytic alveolitis comprised of both CD8+ and CD4+ T cells. Animal models suggest that HP is facilitated by overproduction of IFN-γ, and that IL-10 ameliorates severity of the disease, indicating a Th1-type response. To determine whether a Th1 phenotype in HP also exists clinically, bronchoalveolar lavage (BAL) and peripheral blood (PB) T cells were obtained from HP individuals and analyzed for Th1 vs Th2 cytokine profiles. It was determined that soluble OKT3-stimulated BAL T cells cocultured with alveolar macrophages produced more IFN-γ and less IL-10 than PB T cells cocultured with monocytes, but no difference was observed in IL-4 production. The monocytic cells did not account for this difference, as CD80 and CD86 expressions were similar, and coculturing PB T cells with alveolar macrophages resulted in no difference in IFN-γ production. Similarly, there was no difference in IL-12 production between stimulated BAL or PB T cells; however, addition of rIL-12 significantly increased production of IFN-γ by BAL T cells, but not by PB T cells. This effect was due to a difference in IL-12R expression. High affinity IL-12R were only present in association with BAL T cells. These studies indicate that clinical HP is characterized by a predominance of IFN-γ-producing T cells, perhaps resulting from a reduction in IL-10 production and an increase in high affinity IL-12R compared with blood T cells.

Immune Response duringSaccharopolyspora rectivirgulaInduced Farmer’s Lung Disease

“…Naïve CD4 + T cells encounter antigen and can differentiate into T helper (T H ) subsets such as T H 1, T H 2, T H 9, T H 1 7, T H 22, T follicular cells (T FH ), or T regulatory cells (Tregs) and Type 1 regulatory cells (Tr1), depending on signals from the microenvironment. Previous studies were unable to reach a consensus on which T H cell(s) type are important for disease pathogenesis in FLD [28,74,76,85,86,97,98], however, subsequent studies have found a prominent role for T H 17 cells. The presence of lung lymphocytes and granuloma formation are classic hallmarks of FLD, and CD4 + and CD8 + T cells are found in the BAL of patients with FLD, suggesting they play a role in pathogenesis [79].…”

“…However, when DBA/2 mice are given recombinant IL-12 intranasally, they become sensitive to developing FLD [83]. While BAL and blood samples taken from patients with FLD or summer-type HP had elevated IFN-γ levels, it is unclear whether these were patients who were sensitive to S. rectivirgula [98]. The cellular sources of IFN-γ were likened to neutrophils and a small proportion of NK cells, and in the absence of neutrophils there is a reduction of the severity of alveolitis, although the recruitment of immune cells into the lung following S. rectivirgula is not completely eliminated [28], although more recent work suggest that neutrophils may not be important for the development of inflammation in the lung [102].…”

Hypersensitivity pneumonitis: Current concepts in pathogenesis, diagnosis, and treatment

“…Presentation of foreign antigen by APCs to CD4 + T cells stimulates a predominantly CD4 + Th1 immune response. Correspondingly, presence of lymphocytosis in bronchoalveolar lavage fluid is a useful tool in differentiating HP from other ILDs 37 . This response, mediated by IL‐12 and interferon‐γ, produces CXCL10 to recruit T lymphocytes to the alveolar space, and promote granuloma formation by inducing the functional differentiation and survival of activated macrophages and dendritic cells 38 .…”

“…Correspondingly, presence of lymphocytosis in bronchoalveolar lavage fluid is a useful tool in differentiating HP from other ILDs. 37 This response, mediated by IL-12 and interferonγ, produces CXCL10 to recruit T lymphocytes to the alveolar space, and promote granuloma formation by inducing the functional differentiation and survival of activated macrophages and dendritic cells. 38 The immunologically mediated pathways leading to HP are shared with other granulomatous lung diseases, including chronic beryllium disease and sarcoidosis.…”