CD27 and CD28 coexpression on virus-specific CD8⁺ T cells in HTLV-1 infection. Flow cytometric analysis of CD27 and CD28 coexpression gated on HLA-A*02/Tax11-19 tetramer–positive cells. (A) The model of antigen-specific CD8⁺ T-cell differentiation based on the expression of CD27 and CD28. In the CD8⁺ T-cell population, early differentiated cells differentiate into late-differentiated cells, following a stage of intermediate cells that have down-regulated CD28, but not yet CD27. (B) Dot plots of HLA-A*02/Tax11-19 tetramer-PE (x axis) versus CD8-ECD fluorescence within the lymphocyte gate based on forward versus side scatter. (C) CD28/CD27 expression on total CD8⁺ T-cell– and HTLV-1– or CMV-specific T cells detected by tetramers were shown. The HTLV-1 Tax–specific CD8 T cells were enriched in intermediate-differentiated stage in HVCs and in late-differentiated stage in patients with HAM/TSP, whereas there was no difference in distribution of CMV pp65–specific CD8 T cells between patients with HAM/TSP and HVCs. Representative dot plots from 1 HVC and 1 patient with HAM/TSP for HTLV-1–specific cells, and 1 HAM/TSP patient for CMV-specific cells are shown. (D) Correlation between PVL (y axis; copy number of HTLV-1 tax per 10⁴ PBMCs) and “early,” “intermediate,” or “late” phenotype of HTLV-1 Tax–specific cells (x axis; percentage of Tax-tetramer–positive cells in each subset) in PBMCs from HTLV-1–infected patients. Data were analyzed by Spearman rank correlation.