Immunopathological mechanisms of human T cell lymphotropic virus type 1 (HTLV-I) uveitis. Detection of HTLV-I-infected T cells in the eye and their constitutive cytokine production.
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 out of 94 (59%) or 13 out 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. HTLV-I-infected TCC, but not HTLV-I negative TCC, constitutively produced high amounts of IL-6 (1,336 +/- 1,050 pg/ml) and TNF-alpha (289 +/- 237 pg/ml) in the absence of any stimuli. HTLV-I-infected TCC from the ocular lesion also constitutively produced high amounts of IL-1 alpha (12,699 pg/ml), IL-2 (61 pg/ml), IL-3 (428 pg/ml), IL-8 (1,268 pg/ml), IL-10 (28 pg/ml), IFN-gamma (5,095 pg/ml), and GM-CSF (2,886 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.
Sagawa
K
K
Department of Immunology, Kurume University School of Medicine, Japan.
Mochizuki
M
M
Masuoka
K
K
Katagiri
K
K
Katayama
T
T
Maeda
T
T
Tanimoto
A
A
Sugita
S
S
Watanabe
T
T
Itoh
K
K
D000328:Adult; D001082:Aqueous Humor / Q000276:immunology; D001483:Base Sequence; D001528:Behcet Syndrome / Q000276:immunology / Q000473:pathology / Q000821:virology; D016207:Cytokines / Q000096:biosynthesis*; D017931:DNA Primers; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D015752:Genes, env; D016355:Genes, pX; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D015490:HTLV-I Infections / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000302:isolation & purification* / Q000648:ultrastructure; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014605:Uveitis / Q000276:immunology* / Q000473:pathology* / Q000821:virology
D016207:Cytokines; D017931:DNA Primers; D007378:Interleukins; D012333:RNA, Messenger; D012367:RNA, Viral; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006854:Hydrocortisone