T lymphocyte subset abnormalities in the blood and lung in pulmonary arterial hypertension

Rationale: Mounting data suggest that immune cell abnormalities participate in the pathogenesis of pulmonary arterial hypertension (PAH). Objective: To determine whether the T lymphocyte subset composition in the systemic circulation and peripheral tung is altered in PAH. Methods: Flow cytometric analyses were performed to determine the phenotypic profile of peripheral blood lymphocytes in idiopathic PAH (IPAH) patients (n = 18) and healthy controls (n = 17). Immunocytochemical analyses of lymphocytes and T cell subsets were used to examine lung tissue from PAH patients (n = 11) and controls (n = 11). Measurements and main results: IPAH patients have abnormal CD8+ T lymphocyte subsets, with a significant increase in CD45RA+ CCR7- peripheral cytotoxic effector-memory cells (p = 0.02) and reduction of CD45RA+ CCR7+ naive CD8+ cells versus controls (p = 0.001). Further, IPAH patients have a higher proportion of circulating regulatory T cells (T(reg)) and 4-fold increases in the number of CD3+ and CD8+ cells in the peripheral lung compared with controls (p < 0.01). Conclusions: Alterations in circulating T cell subsets, particularly CD8+ T lymphocytes and CD4+ T(reg), in patients with PAH suggest that a dysfunctional immune system contributes to disease pathogenesis. A preponderance of CD3+ and CD8+ T lymphocytes in the peripheral lung of PAH patients supports this concept. (C) 2009 Elsevier Ltd. All rights reserved.