Oligomannose-coated liposomes efficiently induce human T-cell leukemia virus-1-specific cytotoxic T lymphocytes without adjuvant
Oligomannose-coated liposomes efficiently induce human T-cell leukemia virus-1-specific cytotoxic T lymphocytes without adjuvant
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DOI：
10.1111/j.1742-4658.2011.08055.x
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发表时间：
2011-04-01
期刊：
影响因子：
5.4
通讯作者：
Arima, Naomichi
中科院分区：
文献类型：
--
作者：
Kozako, Tomohiro;Hirata, Shinya;Arima, Naomichi
人类 T 细胞白血病病毒 1 (HTLV-1) 会导致成人 T 细胞白血病/淋巴瘤，这是一种侵袭性外周 T 细胞肿瘤。 T 细胞对 HTLV-1 反应不足是成人 T 细胞白血病/淋巴瘤的潜在危险因素。抗原特异性细胞毒性T淋巴细胞的有效诱导对于病毒感染细胞增殖和肿瘤发生的免疫抑制非常重要，但是抗原特异性细胞毒性T淋巴细胞的有效诱导已经规避了利用免疫原性差的游离合成肽的策略。在这里，我们检查了包裹人类白细胞抗原 (HLA)-A*0201 限制性 HTLV-1 Tax 表位 (OML/Tax) 的寡甘露糖包被脂质体 (OML) 对 HTLV-1 特异性 CD8+ T 细胞反应的有效诱导。用OML/Tax免疫HLA-A*0201转基因小鼠诱导HTLV-1特异性γ-干扰素反应，而单独用表位肽免疫则不诱导反应。将树突状细胞暴露于 OML/Tax 后，CD86、主要组织相容性复合物 I 类、HLA-A02 和主要组织相容性复合物 II 类表达水平增加。此外，我们的结果表明，与单独的表位肽相比，来自 HTLV-1 载体的 OML/Tax 可以有效诱导 HTLV-1 特异性 CD8+ T 细胞，并且这些 HTLV-1 特异性 CD8+ T 细胞能够裂解呈递该肽的细胞。这些结果表明，OML/Tax 能够在没有佐剂的情况下诱导抗原特异性细胞免疫反应，并且可以通过取代表位肽作为有效的疫苗载体来预防肿瘤和传染病。
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)-A*0201-restricted HTLV-1 Tax-epitope (OML/Tax). Immunization of HLA-A*0201 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.