CLONAL EXPANSION OF CD8(+) CYTOTOXIC T-LYMPHOCYTES AGAINST HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I (HTLV-I) GENOME PRODUCTS IN HTLV-I-ASSOCIATED MYELOPATHY TROPICAL SPASTIC PARAPARESIS PATIENTS

Short-term culture of peripheral blood mononuclear cells (PBMC) derived from patients with human T cell lymphotropic virus type I-associated myelopathy (HAM)/tropical spastic paraparesis resulted in dominance by DR(+) activated CD8(+) T cells. Variations in the T cell receptor (TCR) V alpha and V beta chains in these cells were analyzed, and in all 10 patients examined, 2-3 V gene families were dominant in both TCR V alpha and V beta. In five patients we examined, cultured lymphocytes contained cytotoxic lymphocytes for p40(tax) (patients HAM2, 3, 7, and 8) or env protein (patient HAM4) of human T lymphotropic virus type I. In patients HAM2 and HAM8, cultured lymphocytes contained a large proportion of V beta 8(+) CD8(+) and/or V beta 12(+) CD8(+) cells. The sequence of V beta 8(+) and V beta 12(+) cDNA revealed that they were oligoclonal with identical or similar sequences in each patient. Elimination experiments with monoclonal antibodies for TCR V beta 8 and V beta 12 showed that they were CD8(+) cytotoxic T lymphocytes (CTL) for p40(tax). In addition, dow cytometry and sequencing analysis of uncultured PBMC revealed that in HAM2, V beta 8(+) CTL and their precursors account for 7% and V beta 12(+) CTL and their precursors account for 18% of total CD8(+) cells. This indicates the presence of two markedly expanded clones in vivo. No common dominant TCR V alpha or V beta were observed among 10 HAM patients analyzed.