Circulating CD8+ cytotoxic T lymphocytes specific for HTLV-I pX in patients with HTLV-I associated neurological disease

Abstract

THE human T-lymphotropic virus type I (HTLV-I), the first human retrovirus to be characterized, is associated with adult T-cell leukaemia and a chronic progressive disease of the central nervous system termed tropical spastic paraparesis, or HTLV-I-associated myelopathy^1–4. Only 1% of individuals infected with HTLV-I develop clinical disease however⁵. The various manifestations of an HTLV-I infection may be related to differences in the genetic backgrounds of individuals⁶, infection with variant strains of HTLV-I (ref. 7), differences in viral tropism⁸ or host immune response to the virus. Whereas the humoral response to HTLV-I is well characterized^3,4,9,10 little is known about the human cellular immune response, such as the production of cytotoxic T lymphocytes^11–13. Here we report the presence of high levels of circulating HTLV-I-specific cytotoxic T lymphocytes in patients with HTLV-I associated neurological disease but not in HTLV-I seropositive individuals without neurological involvement. These cytotoxic T lymphocytes are CD8⁺, HLA class I- restricted and predominantly recognize the HTLV-I gene products encoded in the regulatory region pX. These findings suggest that HTLV-I-specific cytotoxic T lymphocytes may contribute to the pathogenesis of associated neurological disorders associated with HTLV-I.