Increased killing activity and decreased cytokine production in NK cells in patients with primary biliary cirrhosis.
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 immunoregulatory 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.
Chuang
Ya-Hui
YH
Division of Rheumatology/Allergy and Clinical Immunology, University of California at Davis School of Medicine, 95616, USA.
Lian
Zhe-Xiong
ZX
Tsuneyama
Koichi
K
Chiang
Bor-Luen
BL
Ansari
Aftab A
AA
Coppel
Ross L
RL
Gershwin
M Eric
ME
D000328:Adult; D000368:Aged; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D008875:Middle Aged; D054353:Perforin; D011070:Poly I-C / Q000494:pharmacology; D052899:Pore Forming Cytotoxic Proteins; D023062:Receptors, Interleukin-8A / Q000096:biosynthesis / Q000097:blood / Q000276:immunology
D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D023062:Receptors, Interleukin-8A; D054353:Perforin; D007371:Interferon-gamma; D011070:Poly I-C