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Immunopathological mechanisms of human T-cell lymphotropic virus type 1 (HTLV-I) associated disease. Analysis of T-cell clones from the inflammatory lesions by molecular-immunological methods.

人类 T 细胞嗜淋巴细胞病毒 1 型 (HTLV-I) 相关疾病的免疫病理学机制。

基本信息

批准号：
06670509
负责人：
SAGAWA Kimitaka
金额：
$ 1.41万
依托单位：
Kurume University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

The immunopathology of human T-cell lymphotropic virus type 1 (HTLV-I) uveitis was addressed by using T cell clones (TCC) established from the intraocular fluid of patients with HTLV-I uveitis. Proviral DNA of HTLV-I was identified in 55 of 94 (59%) or 13 of 36 (36%) TCC from the ocular fluid or the peripheral blood of these patients, respectively. Most of HTLV-I-infected TCC had a CD3^+ CD4^+ CD8^- phenotype. HTLV-I infection on TCC was confirmed by analysis of the viral mRNA,nucleotide sequence, virus-associated proteins and virus particles. Furthermore, polyclonal use of T-cell receptor alpha for HTLV-I-infected T cells was detected. HTLV-I-infected TCC,but not HTLV-I negative TCC,constitutively produced high amounts of IL-6 (1336(]SY.+-.])1,050 pg/ml), and TNF-alpha (289(]SY.+-.])237 pg/ml) in the absence of any stimuli. HTLV-I-infected TCC from the ocular lesion also constitutively produced high amounts of IL-1alpha (12699 pg/ml), IL-2 (61 pg/ml), IL-3 (428 pg/ml), IL-8 (1268 pg/ml), IL-10 (28 pg/ml), IFN-gamma (5095 pg/ml), and GM-CSF (2886 pg/ml). Hydrocortisone, a drug effective in vivo for the treatment of HTLV-I uveitis, severely depressed cytokine production in vitro in most cases. In summary, the results demonstrated direct evidence of HTLV-I infection of the eye, and suggest that cytokines produced by HTLV-I-infected T cells are responsible for the intraocular inflammation in patients with HTLV-I uveitis.

通过使用从HTLV-I葡萄膜炎患者的眼内液中建立的T细胞克隆（TCC）来解决人类T细胞嗜淋巴细胞病毒1型（HTLV-I）葡萄膜炎的免疫病理学。从这些患者的眼液或外周血中分别在94例TCC中的55例（59%）或36例TCC中的13例（36%）中鉴定出HTLV-I的前病毒DNA。大多数HTLV-I感染的TCC具有CD 3 ^+ CD 4 ^+ CD 8 ^-表型。通过对病毒mRNA、核苷酸序列、病毒相关蛋白和病毒颗粒的分析，证实了HTLV-Ⅰ对TCC的感染。此外，检测到T细胞受体α对HTLV-I感染的T细胞的多克隆使用。HTLV-I感染的TCC，而不是HTLV-I阴性的TCC，组成性地产生大量的IL-6（1336（[SY. ±.]）1，050 pg/ml）和TNF-α（289（[SY. ±.]）237 pg/ml）。来自眼部病变的HTLV-I感染的TCC也组成性地产生大量的IL-1 α（12699 pg/ml）、IL-2（61 pg/ml）、IL-3（428 pg/ml）、IL-8（1268 pg/ml）、IL-10（28 pg/ml）、IFN-γ（5095 pg/ml）和GM-CSF（2886 pg/ml）。氢化可的松，一种在体内有效治疗HTLV-I葡萄膜炎的药物，在大多数情况下严重抑制体外细胞因子的产生。总之，结果证明了HTLV-I感染眼睛的直接证据，并表明由HTLV-I感染的T细胞产生的细胞因子是HTLV-I葡萄膜炎患者眼内炎症的原因。