The mechanism of immune insufficiency against retroviral tumors and its restoration

已经注意到，成人T细胞白血病（ATL）偶然与母婴感染有关，主要通过母乳建立。在我们的大鼠系统中，口服感染的大鼠表现出显着更高水平的持续性人类T细胞白血病病毒I型（HTLV-I）的负载和更弱的免疫反应，HTLV-I比腹腔感染的大鼠。因此，持续的病毒载量与病毒特异性T细胞应答水平呈负相关。然而，经口感染大鼠的免疫应答不足可以通过皮下重新免疫适当的抗原来恢复。我们还研究了ATL患者的细胞免疫应答，这些患者在来自HLA相同的同胞供体的非清髓性异基因外周血造血干细胞移植（HSCT）后获得完全缓解，并且发现HTLV-I Tax特异性CTL应答在这些患者中的一些患者中在HSCT后而不是HSCT前被强烈激活。这些研究结果表明，在原发性HTLV-I感染时建立的HTLV-I特异性免疫功能不全可能是ATL发展的潜在风险因素，但可以通过免疫策略克服。

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.