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.

利用从HTLV-I型葡萄膜炎患者眼内液中建立的T细胞克隆（TCC）研究了HTLV-I型人T细胞嗜淋巴病毒1型（HTLV-I）葡萄膜炎的免疫病理学。94例TCC中有55例（59%）或36例TCC中有13例（36%）分别检出HTLV-I的前病毒DNA。大多数htlv -i感染的TCC具有CD3^+ CD4^+ CD8^-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htlv - 1感染了TCC。此外，检测了htlv -i感染T细胞的T细胞受体α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.+-）。[1050 pg/ml]), tnf - α (289(]SY.+-。] (237 pg/ml)，在没有任何刺激的情况下。htlv -i感染的眼部病变TCC也组成性地产生大量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）。氢化可的松是一种体内有效治疗HTLV-I型葡萄膜炎的药物，在大多数情况下，在体外严重抑制细胞因子的产生。总之，这些结果提供了HTLV-I感染眼睛的直接证据，并提示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。

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.