Increased Killing Activity and Decreased Cytokine Production in Nk Cells in Patients with Primary Biliary Cirrhosis
Resource
JOURNAL OF AUTOIMMUNITY v.26 n.4 pp.232-240
Journal
JOURNAL OF AUTOIMMUNITY
Journal Volume
v.26
Journal Issue
n.4
Pages
232-240
Date Issued
2006
Date
2006
Author(s)
CHIANG, BOR-LUEN
Abstract
Although the pathogenesis of primary biliary cirrhosis (PBC) remains enigmatic, the immune system plays a key role in the initiation and subsequent development of pathology. Previous studies have indicated a critical role of the innate immune system. Importantly, natural killer (NK ) cells are abundant in liver where they serve as sentinels of the immune system. In addition, NK cells have significant biologic activity based on their production of immumoregulatory cytokines. To address this issue, we have investigated several qualitative and quantitative activities of NK cells in patients with PBC as well as normal and liver diseased controls. We report herein a marked increase in the frequency and absolute number of blood and liver NK cells in PBC patients. Moreover, the cytotoxic activity and perforin expression by isolated NK cells were significantly increased in PBC patients associated with increased levels of plasma IL-8 and the expression of CD128a (IL-8 receptor) on NK cells. In contrast, the levels of IFN-gamma, IL-6 and IL-8 synthesized by NK cells were significantly decreased in PBC patients as compared to controls. In conclusion, data from this study provide compelling evidence supporting a biologic role of NK cells in the immunopathogenesis of PBC.( c) 2006 Elsevier Ltd. All rights reserved.
Subjects
primary biliary cirrhosis (PBC)
natural killer (NK) cells
cytotoxicity
autoimmune liver disease
Type
journal article