Natural killer cells control a T-helper 1 response in patients with Behçet's disease.
BACKGROUND
Behçet's disease (BD) is a multisystem inflammatory disorder, in which a T-helper 1 (Th1)-polarized immune response plays a major role in the pathogenic process. We evaluated the regulatory role of natural killer (NK) cells in Th1-biased immune responses in patients with BD.


METHODS
We studied 47 patients with BD, including 10 with active disease (aBD) and 37 with inactive disease (iBD), and 29 healthy controls. The activation status and cytotoxic activity of NK cells were examined by flow cytometry. The levels of mRNAs for immune modulatory and cytotoxic molecules in NK cells were determined by quantitative PCR. The IL-12 signal strength in NK cells was determined by assessing the phosphorylation state of its downstream component, signal transducer and activator of transduction 4, by immunoblotting. Finally, NK cells' ability to modulate the Th1 response was evaluated by co-culturing NK cells and T cells without cell contact.


RESULTS
CD69+-activated NK cells were significantly increased in aBD compared with iBD or control samples, although their cytotoxic activities were similar. The iBD NK cells showed downregulated IL-12 receptor beta2 mRNA levels compared with aBD or control NK cells. The increased IL-13 expression was detected in a subset of BD patients: most of them had iBD. The IL-13 expression level in iBD patients was significantly higher than the level in controls, but was not statistically different compared with the level in aBD patients. The gene expression profile in iBD patients was consistent with the NK type 2 phenotype, and the shift to NK type 2 was associated with disease remission. NK cells from iBD patients showed impaired IL-12-induced signal transducer and activator of transduction 4 phosphorylation. Finally, iBD, but not control, NK cells suppressed IFNgamma expression by aBD-derived CD4+ T cells in vitro.


CONCLUSIONS
NK cells may control disease flare/remission in BD patients via NK type 2-mediated modulation of the Th1 response.
Yamaguchi
Yukie
Y
Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Takahashi
Hayato
H
Satoh
Takashi
T
Okazaki
Yuka
Y
Mizuki
Nobuhisa
N
Takahashi
Kazuo
K
Ikezawa
Zenro
Z
Kuwana
Masataka
M
D000328:Adult; D001528:Behcet Syndrome / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016022:Case-Control Studies; D002450:Cell Communication / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D053707:Receptors, Interleukin-12 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D018417:Th1 Cells / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology
D018793:Interleukin-13; D053707:Receptors, Interleukin-12; D018664:Interleukin-12; D007371:Interferon-gamma
Clin Exp Rheumatol. 2008 Jul-Aug;26(4 Suppl 50):S59-63
19026117
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