Increased regulatory and decreased CD8+ cytotoxic T cells in the blood of patients with idiopathic pulmonary arterial hypertension.

摘要

BACKGROUND: An association between pulmonary arterial hypertension (PAH) and various immune disorders is well established. Recently, the role of an intact immune system in protecting against pulmonary angioproliferation was shown in an animal model. OBJECTIVE: To elucidate the role of T cells in human PAH, we comparatively studied T cell subclasses with emphasis on regulatory T cells (T(reg)) in the peripheral blood of patients with idiopathic pulmonary arterial hypertension (IPAH) and healthy controls. METHODS: Isolated peripheral blood mononuclear cells from 36 patients diagnosed with IPAH and 33 healthy controls were stained with fluorescently labeled monoclonal antibodies against superficial T cell markers (CD3, CD4, CD8, CD25) and FoxP3, the intracellular marker of T(reg) cells. The relative cell distribution was analyzed by flow cytometry. The functionality of patient and control T(reg) cells was assessed by coculture of T(reg) with nonregulatory T cells from the same individual. RESULTS: Significantly less CD8+ T cells (p = 0.02) and more CD25hi+ and FoxP3+CD4+ T cells were found in the peripheral blood of patients compared with controls (p = 0.009 and p < 0.001, respectively). The percentage of FoxP3+ cells within the CD25hi+CD4+ T(reg) cells was similar. T(reg) cell functionality was equal in patients and controls. CONCLUSION: Our findings of decreased CD8+ T cells and increased T(reg) cells in the peripheral blood of patients with IPAH are novel and may have implications for directing future research in the field to elucidate the differential role of T cells and the immune system in IPAH.