The mechanism of immune insufficiency against retroviral tumors and its restoration

逆转录病毒肿瘤免疫功能低下的机制及其修复

• 批准号: 15023217
• 负责人: KANNAGI Mari
• 金额: $ 10.94万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15023217/
• 关键词: Retovirus; Leukemia; Cytotoxic T lymphocytes; Translational Research; Tumor immunology

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.

人们注意到，成人 T 细胞白血病 (ATL) 与母婴感染偶然相关，大多数是通过母乳传播的。在我们的大鼠系统中，与腹腔内感染的大鼠相比，经口感染的大鼠表现出明显更高水平的持续性人类 T 细胞白血病病毒 I 型 (HTLV-I) 载量，并且对 HTLV-I 的免疫反应要弱得多。因此，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，经口感染的大鼠的免疫反应不足可以通过用适当的抗原进行皮下再免疫来恢复。我们还调查了来自 HLA 相同兄弟供体的非清髓性同种异体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 HTLV-I Tax 特异性 CTL 反应在其中一些患者中在 HSCT 后被强烈激活，但在 HSCT 前则不然。这些发现表明，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 发展的潜在危险因素，但可以通过免疫策略来克服。

项目成果

H.Liu, T.Ohashi, T.Masuda.X.Zhou, M.Kubo, M.Kannagi: "Suppression of HIV-I replication by HIV-I-irrelevant CD8+ cytotoxic T lymphocytes resulting in preservation of persistently HIV-I-infected cells in vitro."Viral Immunology. 16. 381-393 (2003)

H.Liu、T.Ohashi、T.Masuda.X.Zhou、M.Kubo、M.Kannagi：“通过与 HIV-1 无关的 CD8 细胞毒性 T 淋巴细胞抑制 HIV-1 复制，导致持续保存 HIV-1-

Potential immunogenicity of adult T cell leukemia cells in vivo

• DOI: 10.1002/ijc.20737
• 发表时间: 2005-03-20
• 期刊: INTERNATIONAL JOURNAL OF CANCER
• 影响因子: 6.4
• 作者: Kurihara, K;Harashima, N;Kannagi, M
• 通讯作者: Kannagi, M

Future prophylaxis and immunotherapy for adult T cell leukemia.

成人 T 细胞白血病的未来预防和免疫治疗。

• 发表时间: 2004
• 期刊: Expert Review of Anticancer Therapy 4
• 作者: M.Kannagi;et al.
• 通讯作者: et al.

Correlation of major hi stocompatibi1ity complex class I downregulation with resistance of human T cell leukemia virus type I-infected T cells to cytotoxic T-lymphocyte killing in a rat model.

在大鼠模型中，主要组织相容性复合体 I 类下调与人 T 细胞白血病病毒 I 型感染的 T 细胞对细胞毒性 T 淋巴细胞杀伤的抵抗力的相关性。

• 发表时间: 2002
• 期刊: J.Virol. 76
• 作者: T.Ohashi;S.Hanabuchi;R.Suzuki;H.Kato;H.Tateno;T.Masuda;M.Kannagi.
• 通讯作者: M.Kannagi.

Correlation of major histocompatibility complex class I downregulation with resistance of human T cell leukemia virus type I-infected T cells to cytotoxic T-lymphocyte killing in a rat model.

在大鼠模型中，主要组织相容性复合物 I 类下调与人 T 细胞白血病病毒 I 型感染的 T 细胞对细胞毒性 T 淋巴细胞杀伤的抵抗力的相关性。

• 发表时间: 2002
• 期刊: J.Virol. 76
• 作者: T.Ohashi;et al.
• 通讯作者: et al.