Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Retrovirology. 2013 Feb 13;10:19. doi: 10.1186/1742-4690-10-19.
Human T cell lymphotropic virus type 1 (HTLV-1) infection can lead to development of adult T cell leukemia/lymphoma (ATL) or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a subset of infected subjects. HTLV-1 basic leucine zipper factor (HBZ) gene has a critical role in HTLV-1 infectivity and the development of ATL and HAM/TSP. However, little is known about the immune response against HBZ in HTLV-1-infected individuals. In this study, we examined antibody responses against HBZ in serum/plasma samples from 436 subjects including HTLV-1 seronegative donors, asymptomatic carriers (AC), ATL, and HAM/TSP patients using the luciferase immunoprecipitation system.
Immunoreactivity against HBZ was detected in subsets of all HTLV-1-infected individuals but the test did not discriminate between AC, ATL and HAM/TSP. However, the frequency of detection of HBZ-specific antibodies in the serum of ATL patients with the chronic subtype was higher than in ATL patients with the lymphomatous subtype. Antibody responses against HBZ were also detected in cerebrospinal fluid of HAM/TSP patients with anti-HBZ in serum. Antibody responses against HBZ did not correlate with proviral load and HBZ mRNA expression in HAM/TSP patients, but the presence of an HBZ-specific response was associated with reduced CD4+ T cell activation in HAM/TSP patients. Moreover, HBZ-specific antibody inhibited lymphoproliferation in the PBMC of HAM/TSP patients.
This is the first report demonstrating humoral immune response against HBZ associated with HTLV-I infection. Thus, a humoral immune response against HBZ might play a role in HTLV-1 infection.
人类 T 细胞白血病病毒 1 型（HTLV-1）感染可导致部分感染者发生成人 T 细胞白血病/淋巴瘤（ATL）或 HTLV-1 相关脊髓病/热带痉挛性截瘫（HAM/TSP）。HTLV-1 碱性亮氨酸拉链因子（HBZ）基因在 HTLV-1 感染性、ATL 和 HAM/TSP 的发生发展中具有关键作用。然而，目前对于 HTLV-1 感染者针对 HBZ 的免疫反应知之甚少。在这项研究中，我们使用荧光素酶免疫沉淀系统，检测了来自 436 名受试者（包括 HTLV-1 血清阴性供体、无症状携带者（AC）、ATL 和 HAM/TSP 患者）血清/血浆样本中针对 HBZ 的抗体反应。
所有 HTLV-1 感染者的亚群中均检测到针对 HBZ 的免疫反应，但该检测不能区分 AC、ATL 和 HAM/TSP。然而，慢性亚型 ATL 患者血清中 HBZ 特异性抗体的检出频率高于淋巴母细胞型 ATL 患者。血清中存在抗 HBZ 的 HAM/TSP 患者的脑脊液中也检测到针对 HBZ 的抗体反应。针对 HBZ 的抗体反应与 HAM/TSP 患者的前病毒载量和 HBZ mRNA 表达无关，但在 HAM/TSP 患者中，存在 HBZ 特异性反应与 CD4+T 细胞活化减少相关。此外，HBZ 特异性抗体抑制了 HAM/TSP 患者 PBMC 的淋巴增殖。
这是第一项证明与 HTLV-I 感染相关的针对 HBZ 的体液免疫反应的报告。因此，针对 HBZ 的体液免疫反应可能在 HTLV-1 感染中发挥作用。
