Reduced frequency, diversity, and function of human T cell leukemia virus type 1-specific CD8+ T cell in adult T cell leukemia patients

Human T cell lymphotropic virus type 1 (HTLV-1)-specific CTL are thought to be immune effectors that reduce the risk of adult T cell leukemia (ATL). However, in vivo conditions of anti-HTLV-1 CTL before and after ATL development have yet to be determined. To characterize anti-HTLV-1 CTL in asymptomatic HTLV-1 carriers (AC) and ATL patients, we analyzed the frequency and diversity of HTLV-1-specific CD8(+) T cells in PBMC of 35 AC and 32 ATL patients using 16 distinct epitopes of HTLV-1 Tax or Env/HLA tetramers along with intracellular cytolytic effector molecules (IFN-gamma, perforin, and granzyme B). Overall frequency of subjects possessing Tax-specific CD8+ T cells was significantly lower in ATL than AC (53 vs 90%; p = 0.001), whereas the difference in Env-specific CD8(+) T cells was not statistically significant. AC possessed Tax(11-19)/HLA-A*0201-specific tetramer(+) cells by 90% and Tax(301-309)/HLA-A*2402-specific tetramer(+) cells by 92%. Some AC recognized more than one epitope. In contrast, ATL recognized only Tax(11-19) with HLA-A*0201 and Tax(301-309) with HLA-A*2402 at frequencies of 30 and 55%. There were also significant differences in percentage of cells binding Tax(11-19)/HLA-A*0201 and Tax(301-309)/HLA-A*2402 tetramers between AC and ATL. Anti-HTLV-1 Tax CD8(+) T cells in AC and ATL produced IFN-gamma in response to Tax. In contrast, perforin and granzyme B expression in anti-HTLV-1 CD8(+) T cells of ATL was significant lower than that of AC. Frequency of Tax-specific CD8(+) T cells in AC was related to proviral load in HLA-A*0201. These results suggest that decreased frequency, diversity, and function of anti-HTLV-1 Tax CD8(+) T cell clones maybe one of the risks of ATL development.