The mechanism of immune insufficiency against retroviral tumors and its restoration

点击翻译按钮获取中文摘要

It has been noted that adult T-cell leukemia (ATL) is incidentally associated with mother-to-child infection, mostly established via mother milk. In our rat system, orally infected rats exhibited significantly higher levels of persistent human T-cell leukemia virus type I (HTLV-I) load and much weaker immune response to HTLV-I than that in intraperitoneally infected rats. As a result, persistent viral load was inversely correlated with levels of virus-specific T-cell responses. The insufficient immune responses in orally infected rats could be, however, recovered by subcutaneous re-immunization with appropriate antigens. We also investigated cellular immune responses of ATL patients who obtained complete remission following non-myeloablative allogeneic peripheral blood hematopoietic stem cell transplantation (HSCT) from HLA-identical sibling donors, and found that HTLV-I Tax-specific CTL response was strongly activated in some of these patients post-HSCT but not before HSCT. These findings suggest that HTLV-I-specific immune insufficiency established at primary HTLV-I infection may be an underlying risk factor for development of ATL, but could be overcome with immunological strategies.