Supplementary Material for: A Familial History of Pulmonary Fibrosis in Patients with Chronic Hypersensitivity Pneumonitis

<b><i>Background:</i></b> Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease induced by the inhalation of a variety of antigens. Patients with chronic HP often have a family history of pulmonary fibrosis. This strongly suggests that both genetic and environmental factors play an important role in the pathogenesis of chronic HP. <b><i>Objectives:</i></b> We aimed to investigate the epidemiology and clinical features of chronic HP patients with a family history of pulmonary fibrosis. <b><i>Methods:</i></b> We retrospectively reviewed the clinical information of 114 cases diagnosed with chronic HP with insidious onset between 1992 and 2009. <b><i>Results:</i></b> Twenty cases (17.5%) were identified as having a family history of pulmonary fibrosis. All of these patients had lived apart from their afflicted relatives for at least several decades. The familial cases were younger than the nonfamilial cases at onset (57.5 ± 9.6 vs. 64.0 ± 7.0 years old, p = 0.008). The predicted vital capacity percentage and partial pressure of oxygen in arterial blood gas were significantly higher in the familial cases. There were no differences between the 2 groups in gender, smoking history, bronchoalveolar lavage fluid profile, radiologic findings or other clinical features. <b><i>Conclusions:</i></b> We found a familial clustering in patients with chronic HP. Various factors including genetic susceptibility to pulmonary fibrosis and environmental factors may contribute to the development of familial chronic HP

Supplementary Material for: Potential Role of Gr-1⁺ CD8⁺ T Lymphocytes as a Source of Interferon-γ and M1/M2 Polarization during the Acute Phase of Murine <b><i>Legionella pneumophila</i></b> Pneumonia

In this study, we analyzed interferon (IFN)-γ-producing cells and M1/M2 macrophage polarization in <i>Legionella pneumophila</i> pneumonia following anti-Gr-1 antibody treatment. Anti-Gr-1 treatment induced an M1-to-M2 shift of macrophage subtypes in the lungs and weakly in the peripheral blood, which was associated with increased mortality in legionella-infected mice. CD8⁺ T lymphocytes and natural killer cells were the dominant sources of IFN-γ in the acute phase, and anti-Gr-1 treatment reduced the number of IFN-γ-producing CD8⁺ T lymphocytes. In the CD3-gated population, most Gr-1-positive cells were CD8⁺ T lymphocytes in the lungs and lymph nodes (LNs) of infected mice. Additionally, the number of IFN-γ-producing Gr-1⁺ CD8⁺ T lymphocytes in the lungs and LNs increased 2 and 4 days after <i>L. pneumophila</i> infection, with anti-Gr-1 treatment attenuating these populations. Antibody staining revealed that Gr-1⁺ CD8⁺ T lymphocytes were Ly6C-positive cells rather than Ly6G, a phenotype regarded as memory type cells. Furthermore, the adoptive transfer of Gr-1⁺ CD8⁺ T lymphocytes induced increases in IFN-γ, M1 shifting and reduced bacterial number in the <i>Legionella</i> pneumonia model. These data identified Ly6C⁺ CD8⁺ T lymphocytes as a source of IFN-γ in innate immunity and partially associated with reduced IFN-γ production, M2 polarization, and high mortality in anti-Gr-1 antibody-treated mice with <i>L. pneumophila</i> pneumonia