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

• Published in: Nature (London) 1990-11, Vol.348 (6298), p.245-248
• Main Authors: JACOBSON, S, SHIDA, H, MCFARLIN, D. E, FAUCI, A. S, KOENIG, S
• Format: Article
• Language: English
• Subjects: Adult; AIDS/HIV; Biochemistry; Biological and medical sciences; CD8 antigen; Cell Line, Transformed; Cellular manufacture; Central nervous system; Cytotoxicity; Disease; DNA, Recombinant; Female; Gene Expression; Gene Products, env - genetics; Gene Products, env - immunology; Gene Products, rex - genetics; Gene Products, rex - immunology; Gene Products, tax - genetics; Gene Products, tax - immunology; Hereditary spastic paraplegia; Histocompatibility antigen HLA; HTLV-I Infections - immunology; Human behavior; Human T-lymphotropic virus 1 - genetics; Human T-lymphotropic virus 1 - immunology; Human viral diseases; Humans; Immune response; Immune response (cell-mediated); Immune response (humoral); Immune system; Infections; Infectious diseases; Leukemia; Leukemia, T-Cell - immunology; Lymphocytes; Lymphocytes T; Male; Medical sciences; Middle Aged; Nervous system; Neurological diseases; Neurological disorders; Paraparesis, Tropical Spastic - immunology; Pathogenesis; Patients; Proteins; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Regulatory - immunology; Transfection; Tropical spastic paraparesis; Vaccinia virus - genetics; Viral diseases; Viral diseases of the nervous system; Viral infections; Viruses
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/348245a0

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. Only 1% of individuals infected with HTLV-I develop clinical disease however. The various manifestations of an HTLV-I infection may be related to differences in the genetic backgrounds of individuals, infection with variant strains of HTLV-I, differences in viral tropism or host immune response to the virus. Whereas the humoral response to HTLV-I is well characterized, little is known about the human cellular immune response, such as the production of cytotoxic T lymphocytes. 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.