Modulation of T cell responses in HTLV-1 carriers and in patients with myelopathy associated with HTLV-1.
Modulation of T cell responses in HTLV-1 carriers and in patients with myelopathy associated with HTLV-1.
复制标题
HTLV-1 携带者和 HTLV-1 相关脊髓病患者 T 细胞反应的调节。
DOI：
10.1159/000097259
复制
发表时间：
2006
影响因子：
2.4
通讯作者：
Carvalho,EdgarM
中科院分区：
文献类型：
--
作者：
Santos,SilvaneB;Porto,AureliaF;Muniz,AndreLuiz;Luna,Tania;Nascimento,MarciaC;Guerreiro,JaquelineB;Oliveira-Filho,Jamary;Morgan,DanielJ;Carvalho,EdgarM
目的：人类嗜T淋巴细胞病毒1型（HTLV-1）可激活免疫系统，导致持续和加剧的T细胞反应，并增加IFN-γ和TNF-α的产生。促炎细胞因子的过度产生与HTLV-1相关的脊髓病/热带痉挛性下肢轻瘫（HAM/TSP）的发展相关，尽管一些HTLV-1携带者也显示出高水平的这些细胞因子。方法：采用ELISA法检测细胞因子或抗细胞因子加入前后IFN-γ的水平。结果：加入IL-10可显著降低HTLV-1携带者细胞IFN-γ的自发合成，而HAM/TSP患者细胞IFN-γ的自发合成无明显差异。在外源性添加TGF-β的情况下，来自HTLV-1携带者的细胞培养物中的IFN-γ水平也有降低的趋势。在配对分析中，中和IL-2可显著降低HTLV-1携带者IFN-γ的产生，但在HAM/TSP患者中则无此作用。IL-15的中和在调节IFN-γ产生方面不如IL-2的中和有效。在HTLV-1携带者中，抗IL-2和同时加入抗IL-2和抗IL-15分别使IFN-γ合成降低46%和64%，而在HAM/TSP患者中，同时中和两种抗细胞因子仅使IFN-γ水平降低27%。尽管大部分HTLV-1携带者产生与HAM/TSP患者中观察到的类似的高水平促炎细胞因子，在大多数HTLV-1携带者中，免疫应答可被细胞因子或细胞因子拮抗剂下调。这种调节可以是预防组织损伤和从HTLV-1携带者状态进展为HAM/TSP的重要步骤。
Objective:Human T lymphotropic virus-type 1 (HTLV-1) activates the immune system leading to a persistent and exacerbated T-cell response with increased production of IFN-γ and TNF-α. Overproduction of pro-inflammatory cytokines is correlated with the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), although some HTLV-1 carriers also show high levels of these cytokines. In this study, the ability of regulatory cytokines and cytokine antagonists to inhibit spontaneous IFN-γ production was investigated.Method:IFN-γ levels were measured by ELISA before and after addition of cytokines or anti-cytokines.Results:Addition of IL-10 significantly reduced spontaneous IFN-γ synthesis in cell cultures from HTLV-1 carriers, while no differences were observed in HAM/TSP patients. There was also a tendency to decreased IFN-γ levels in cell cultures from HTLV-1 carriers with exogenous addition of TGF-β. In paired analysis, neutralization of IL-2 significantly decreased IFN-γ production in HTLV-1 carriers but not in HAM/TSP patients. Neutralization of IL-15 was less effective than neutralization of IL-2 in modulating IFN-γ production. In HTLV-1 carriers, anti-IL-2 and simultaneous addition of anti-IL-2 and anti-IL-15 decreased IFN-γ synthesis by 46 and 64%, respectively, whereas in patients with HAM/TSP simultaneous neutralization of both anti-cytokines only decrease IFN-γ levels by 27%.Conclusions:Although a large proportion of HTLV-1 carriers produced high levels of pro-inflammatory cytokines similar to those observed in HAM/TSP patients, immune response can be downregulated by cytokines or cytokine antagonists in most HTLV-1 carriers. This modulation can be an important step in the prevention of tissue damage and progression from the HTLV-1 carrier state to HAM/TSP.