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

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) Vα and Vβ chains in these cells were analyzed, and in all 10 patients examined, 2-3 V gene families were dominant in both TCR Vα and Vβ. 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 Vβ8+ CD8+ and/or Vβ12+ CD8+ cells. The sequence of Vβ8+ and Vβ12+ cDNA revealed that they were oligoclonal with identical or similar sequences in each patient. Elimination experiments with monoclonal antibodies for TCR Vβ8 and Vβ12 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, Vβ8+ CTL and their precursors account for 7% and Vβ12+ 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 Va or Vβ were observed among 10 HAM patients analyzed.