| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
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.
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