natural killer cells control a t-helper 1 response in patients with beh？ets disease自然杀伤细胞控制辅助1响应患者的本·等的疾病.pdfVIP

Yamaguchi et al. Arthritis Research Therapy 2010, 12:R80 /content/12/3/R80 R E S E A R C H A R T I C L E Open Access Research article Natural killer cells control a T-helper 1 response in patients with Behçets disease 1,2 3 1 1 4 2 Yukie Yamaguchi , Hayato Takahashi , Takashi Satoh , Yuka Okazaki , Nobuhisa Mizuki , Kazuo Takahashi , 2 1 Zenro Ikezawa and Masataka Kuwana* Abstract Introduction: Behçets 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 β2 mRNA levels compared with aBD or control NK cells. The increased IL-13 expression was detected in a subset of BD patients