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


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Abstract

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) Valpha and Vbeta chains in these cells were analyzed, and in all 10 patients examined, 2-3 V gene families were dominant in both TCR Valpha and Vbeta. In five patients we examined, cultured lymphocytes contained cytotoxic lymphocytes for p40tax (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 Vbeta8+ CD8 (+) and/or Vbeta12+ CD8+ cells. The sequence of Vbeta8+ and Vbeta12+ cDNA revealed that they were oligoclonal with identical or similar sequences in each patient. Elimination experiments with monoclonal antibodies for TCR Vbeta8 and Vbeta12 showed that they were CD8+ cytotoxic T lymphocytes (CTL) for p40tax. In addition, flow cytometry and sequencing analysis of uncultured PBMC revealed that in HAM2, Vbeta8+ CTL and their precursors account for 7% and Vbeta12+ 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 Valpha or Vbeta were observed among 10 HAM patients analyzed. (J. Clin. Invest. 1994. 94:1830-1839.) Key words: T cell receptor. Vbeta gene. tax protein. cell-mediated cytotoxicity. polymerase chain reaction

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