Protective effect of cytotoxic T lymphocytes targeting HTLV-1 bZIP factor

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia-lymphoma (ATL) and inflammatory diseases in a small percentage of infected individuals. Host immune responses, in particular cytotoxic T lymphocytes (CTLs), influence the proliferation and survival of ATL cells and HTLV-1-infected cells. We generated recombinant vaccinia viruses (rVVs) expressing HTLV-1 basic leucine zipper (bZIP) factor (HBZ) or Tax to study the immunogenic potential of these viral proteins. Vaccination with rVV expressing Tax or HBZ induced specific T-cell responses, although multiple boosters were needed for HBZ. HBZ-stimulated T cells killed HBZ peptide-pulsed T cells and CD4+ T cells from HBZ transgenic (HBZ-Tg) mice. The anti-lymphoma effect of the CTLs targeting HBZ was tested in mice inoculated with a lymphoma cell line derived from an HBZ-Tg mouse. Transfer of splenocytes from HBZ-immunized mice increased the survival of the lymphoma cell-inoculated mice, suggesting that the anti-HBZ CTLs have a protective effect. The rVV could also induce specific T-cell responses to HBZ and Tax in HTLV-1-infected rhesus monkeys. On the basis of the results of rVV-vaccinated mice and macaques, we identified a candidate peptide (HBZ157-176) for vaccine development. Dendritic cells pulsed with this peptide could generate HBZ-specific CTLs from human CD8+ T cells. This study demonstrates that HBZ could be a target for immunotherapy of patients with ATL.