The mechanism of immune insufficiency against retroviral tumors and its restoration

人们注意到，成人T细胞白血病(ATL)与母婴感染有关，主要是通过母乳感染。在我们的大鼠系统中，口服感染的大鼠的持续人类T细胞白血病病毒I型(HTLV-I)载量显著高于腹腔感染的大鼠，而对HTLV-I的免疫反应明显弱于腹腔感染的大鼠。结果，持续病毒载量与病毒特异性T细胞反应水平呈负相关。然而，口服感染的大鼠的免疫反应不足可以通过皮下注射适当的抗原来恢复。我们还研究了非清髓性异基因外周血造血干细胞移植(HSCT)后获得完全缓解的ATL患者的细胞免疫反应，发现其中一些患者在HSCT后但在HSCT前没有强烈激活HTLV-I抗原特异性CTL反应。这些发现表明，在初次HTLV-I感染时建立的HTLV-I特异性免疫不足可能是ATL发生的潜在危险因素，但可以通过免疫学策略来克服。

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.