Natural killer cells control a T-helper 1 response in patients with Behçet's disease
نویسندگان
چکیده
INTRODUCTION 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.
منابع مشابه
Behçet's Disease Long Time after Sulfur Mustard Poisoning
Dear Editor, A 35-year-old man presented with severe headache and left sided hemiparesis since one day prior to admission. He reported frequent bouts of oral and genital aphthous ulcers, an attack of deep venous thrombosis of left lower extremity, one episode of right knee arthritis, and several attacks of headache, neck rigidity, and fever. He had been a victim of mustard-gas poisoning at the ...
متن کاملبررسی فتوتیپهای سلولیNatural killer (NK) و سلولهای شبه Natural killer T(NKT) در بیماران مبتلا به زخم پپتیک و سرطان معدهی ناشی از عفونت هلیکوباکتر پیلوری
Background and purpose: The aim of this study was to compare the proportion of natural killer (NK) and natural killer T (NKT)-like cells in dyspeptic disorders caused by Helicobacter pylori (H. pylori). Materials and methods: In a case-control study, 27 patients with gastric cancer (GC), 25 patients with peptic ulcer (PUD), and 22 patients with non-ulcer dyspepsia (NUD) were enrolled. After en...
متن کاملComparison of Th1 and Th2 Responses in Non-Healing and Healing Patients with Cutaneous Leishmaniasis
Background: Cutaneous leishmaniasis is an endemic disease in many regions of Iran, including the city of Mashhad. In recent years, some cases have not responded to Glucantime, the usual treatment for this disease. The cellular immune response caused by T-helper type 1 (Th1) cells has an important role in protection against leishmaniasis, and activation of the T-helper type 2 (Th2) response caus...
متن کاملCD56+ T cells in the peripheral blood of uveitis patients.
AIMS Natural killer T (NKT) cells, T lymphocytes expressing both T cell and NK cell markers, are suggested to be involved in autoimmune diseases. To examine the relation between the pathogenesis of uveitis and CD56+ T cells, which are thought to be a type of human NKT cells, we investigated peripheral CD56+ T cells in uveitis patients. METHODS 41 uveitis patients (Behçet's disease (BD), 14; s...
متن کاملThe Yin and Yang of Invariant Natural Killer T Cells in Tumor Immunity—Suppression of Tumor Immunity in the Intestine
CD1d-restricted invariant natural killer T (iNKT) cells are known as early responding, potent regulatory cells of immune responses. Besides their established role in the regulation of inflammation and autoimmune disease, numerous studies have shown that iNKT cells have important functions in tumor immunosurveillance and control of tumor metastasis. Tumor-infiltrating T helper 1 (TH1)/cytotoxic ...
متن کامل