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寡甘露糖包覆的脂质体在无佐剂的情况下有效诱导人 T 细胞白血病病毒 1 特异性细胞毒性 T 淋巴细胞。

Oligomannose-coated liposomes efficiently induce human T-cell leukemia virus-1-specific cytotoxic T lymphocytes without adjuvant.

机构信息

Division of Hematology and Immunology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.

出版信息

FEBS J. 2011 Apr;278(8):1358-66. doi: 10.1111/j.1742-4658.2011.08055.x. Epub 2011 Mar 10.

DOI:10.1111/j.1742-4658.2011.08055.x
PMID:21332943
Abstract

Human T-cell leukemia virus-1 (HTLV-1) causes adult T-cell leukemia/lymphoma, which is an aggressive peripheral T-cell neoplasm. Insufficient T-cell response to HTLV-1 is a potential risk factor in adult T-cell leukemia/lymphoma. Efficient induction of antigen-specific cytotoxic T lymphocytes is important for immunological suppression of virus-infected cell proliferation and oncogenesis, but efficient induction of antigen-specific cytotoxic T lymphocytes has evaded strategies utilizing poorly immunogenic free synthetic peptides. Here, we examined the efficient induction of an HTLV-1-specific CD8+ T-cell response by oligomannose-coated liposomes (OMLs) encapsulating the human leukocyte antigen (HLA)-A0201-restricted HTLV-1 Tax-epitope (OML/Tax). Immunization of HLA-A0201 transgenic mice with OML/Tax induced an HTLV-1-specific gamma-interferon reaction, whereas immunization with epitope peptide alone induced no reaction. Upon exposure of dendritic cells to OML/Tax, the levels of CD86, major histocompatibility complex class I, HLA-A02 and major histocompatibility complex class II expression were increased. In addition, our results showed that HTLV-1-specific CD8+ T cells can be efficiently induced by OML/Tax from HTLV-1 carriers compared with epitope peptide alone, and these HTLV-1-specific CD8+ T cells were able to lyse cells presenting the peptide. These results suggest that OML/Tax is capable of inducing antigen-specific cellular immune responses without adjuvants and may be useful as an effective vaccine carrier for prophylaxis in tumors and infectious diseases by substituting the epitope peptide.

摘要

人 T 细胞白血病病毒-1(HTLV-1)引起成人 T 细胞白血病/淋巴瘤,这是一种侵袭性外周 T 细胞肿瘤。对 HTLV-1 的 T 细胞反应不足是成人 T 细胞白血病/淋巴瘤的一个潜在危险因素。诱导抗原特异性细胞毒性 T 淋巴细胞的效率对于抑制病毒感染细胞的增殖和肿瘤发生的免疫非常重要,但利用免疫原性差的游离合成肽诱导抗原特异性细胞毒性 T 淋巴细胞的效率一直难以实现。在这里,我们研究了包裹人白细胞抗原(HLA)-A0201 限制性 HTLV-1 Tax-表位的寡甘露糖涂层的脂质体(OML/Tax)对 HTLV-1 特异性 CD8+T 细胞反应的有效诱导。用 OML/Tax 免疫 HLA-A0201 转基因小鼠可诱导 HTLV-1 特异性γ干扰素反应,而单独用表位肽免疫则无反应。树突状细胞暴露于 OML/Tax 后,CD86、主要组织相容性复合体 I 类、HLA-A02 和主要组织相容性复合体 II 类的表达水平增加。此外,我们的结果表明,与单独使用表位肽相比,OML/Tax 能够从 HTLV-1 携带者中有效诱导 HTLV-1 特异性 CD8+T 细胞,并且这些 HTLV-1 特异性 CD8+T 细胞能够裂解呈递肽的细胞。这些结果表明,OML/Tax 无需佐剂即可诱导抗原特异性细胞免疫应答,并且可能通过替代表位肽作为预防肿瘤和传染病的有效疫苗载体而具有应用前景。

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