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.

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 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, virusassociated proteins, and virus particles. HTLV-I-infected TCC, but not HTLV-I negative TCC, constitutively produced high amounts of (1,336±1,050 pg/ml) and TNFa (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-la (12,699 pg/ml), IL-2 (61 pg/ml), IL-3 (428 pglml), (1,268 pg/ml), IL-10 (28 pg/ ml), IFN-y (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. (J. Clin. Invest. 1995. 95:852-858.)

Human T lymphotropic virus type I in arthropathy and autoimmune disorders

“…Furthermore, T cell clones established from aflected lesions were CD3+,CD4+,CD8+ phenotypically, and these clones constitutively produced high amounts of IL-6 and TNFa. The investigators proposed the presence of activated autoreactive T cells recognizing certain retinal antigens (51). This suggestion is consistent with our findings that restricted HTLV-I-infected T cell clones proliferate and expand in the lesions of HTLV-I arthropathy and bchave as autoreactive T cells (48).…”

Genetic control and dynamics of the cellular immune response to the human T–cell leukaemia virus, HTLV–I

“…HTLV-I is also associated with chronic or subacute in£ammatory diseases in the eye (Sagawa et al 1995), lung (Higashiyama et al 1994) and skeletal muscles (Morgan et al 1989;Higuchi et al 1996). There are also suggestions of similar conditions in the skin (LaGrenade et al 1990), joints (Nishioka et al 1989) and liver, but these associations are less certain.…”

AZT inhibits the transmission of human T cell leukaemia/lymphoma virus type I to adult peripheral blood mononuclear cells in vitro.

“…More recently, HTLV-I was also found to be associated with neurological syndromes, particularly HTLV-I associated human myelopathies in Japan and tropical spastic paraparesis in South America (Osame et al, 1986 ;Jacobson et al, 1988), in uveitis and arthropathies (Sagawa et al, 1995 ;Nishioka et al, 1989). In vivo, virus transmission can be either horizontal and\or vertical, and usually results from blood exchange (Okochi et al, 1984 ;Osame et al, 1986 b) or breast feeding (from mother to child) (Hino et al, 1985).…”