Fukushima Naomi, Nishiura Yoshihiro, Nakamura Tatsufumi, Kohno Shigeru, Eguchi Katsumi
Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Intern Med. 2007;46(7):347-51. doi: 10.2169/internalmedicine.46.6118. Epub 2007 Apr 2.
Th1 activation based on a high HTLV-I proviral load is one of the characteristic immunological abnormalities in the peripheral blood lymphocytes of patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). To clarify the cause of this abnormality with the potential to be one of the therapeutic targets, we analyzed the involvement of interleukin-2 (IL-2)/IL-2 receptor (IL-2R) signaling in HTLV-I and interferon-gamma (IFN-gamma), which is a representative Th1 cytokine, expression in peripheral blood CD4(+) T cells from HAM/TSP patients.
Twelve patients with HAM/TSP were included in the study. After the peripheral blood CD4(+) T cells were treated in cultures under the presence of each anti-IL-2Ralpha, beta,and gamma blocking antiboby for 48 hours, both HTLV-I p19 antigen and IFN-gamma levels in the culture supernatants were measured using ELISA methods. To check the influence on cell proliferation under these culture conditions, the numbers of viable cells were simultaneously determined by MTS assay.
Treatment with anti-IL-2Ralpha blocking antibody, but not anti-IL-2Rbeta or anti-IL-2Rgamma blocking antibody, suppressed HTLV-I p19 antigen expression levels. In addition, treatment with all types of anti-IL-2R blocking antibodies also suppressed IFN-gamma expression levels. All of the types of anti-IL-2R blocking antibodies did not inhibit the proliferation.
These results indicate that IL-2/IL-2R signaling is involved in HTLV-I and IFN-gamma expression on peripheral blood CD4(+) T cells from HAM/TSP patients, suggesting that the interruption of this signaling has therapeutic potential against HAM/TSP in patients with the focus on the down-regulation of Th1 activation based on a high HTLV-I proviral load in the peripheral blood.
基于高人类嗜T淋巴细胞病毒I型（HTLV-I）前病毒载量的Th1激活是HTLV-I相关脊髓病/热带痉挛性截瘫（HAM/TSP）患者外周血淋巴细胞特征性免疫异常之一。为阐明这一可能成为治疗靶点的异常原因，我们分析了白细胞介素-2（IL-2）/IL-2受体（IL-2R）信号通路在HTLV-I及干扰素-γ（IFN-γ，一种代表性的Th1细胞因子）在HAM/TSP患者外周血CD4(+) T细胞中表达的影响。
12例HAM/TSP患者纳入本研究。外周血CD4(+) T细胞在每种抗IL-2Rα、β和γ阻断抗体存在的培养条件下处理48小时后，使用酶联免疫吸附测定（ELISA）方法检测培养上清液中HTLV-I p19抗原和IFN-γ水平。为检测这些培养条件下对细胞增殖的影响，通过MTS检测同时测定活细胞数量。
抗IL-2Rα阻断抗体处理可抑制HTLV-I p19抗原表达水平，而抗IL-2Rβ或抗IL-2Rγ阻断抗体处理则无此作用。此外，所有类型的抗IL-2R阻断抗体处理均抑制IFN-γ表达水平。所有类型的抗IL-2R阻断抗体均未抑制细胞增殖。
这些结果表明，IL-2/IL-2R信号通路参与了HAM/TSP患者外周血CD4(+) T细胞中HTLV-I和IFN-γ的表达，提示中断该信号通路可能对HAM/TSP患者具有治疗潜力，尤其关注基于外周血中高HTLV-I前病毒载量下调Th1激活。
