Selected cytotoxic T lymphocytes with high specicity for HTLV-I in cerebrospinal uid from a HAM/TSP patient

Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inammatory disease of the spinal cord in which HTLV-I Tax-speciŽc cytotoxic T lymphocytes (CTL) have been suggested to be immunopathogenic. However, it is unknownwhether the HTLVI-speciŽc CTL in the central nervous system differ from those in the periphery. We investigated functional T-cell receptor diversity in HTLV-I Tax11-19speciŽc CTL clones derived from peripheral blood and cerebrospinal uid (CSF) of a HAM/TSP patient using analogue peptides of the viral antigen. CTL responses to the analogue peptides varied between T-cell clones, however, CTL clones from CSF showed limited recognition of the peptides when compared to those from peripheral blood. This suggests that CTL with highly focused speciŽcity for HTLV-I Tax accumulate in the CSF and may contribute to the pathogenesis of HAM/TSP. Furthermore, this study provides a rationale for analogue peptide-based immunotherapeutic strategies focusing on the immunopathogenic T-cells in HTLV-I-associated neurologic disease. Journal of NeuroVirology (2002) 8, 53–57.