Direct recognition and lysis of leukemia cells by WT1-specific CD4+ T lymphocytes in an HLA class II-restricted manner
Direct recognition and lysis of leukemia cells by WT1-specific CD4+ T lymphocytes in an HLA class II-restricted manner
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DOI：
10.1182/blood-2005-01-0413
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发表时间：
2005-08-15
期刊：
影响因子：
20.3
通讯作者：
Yasukawa, M
中科院分区：
文献类型：
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作者：
Guo, Y;Niiya, H;Yasukawa, M
肾母细胞瘤基因1产物（WT 1）已被公认为是包括白血病在内的多种恶性肿瘤免疫治疗的有吸引力的靶抗原。由于肿瘤相关抗原特异性CD 4（+）T淋巴细胞无疑在诱导抗肿瘤免疫应答中起重要作用，我们尝试在体外产生WT 1特异性CD 4（+）T淋巴细胞并检测其抗白血病功能。建立了命名为NIK-1的CD 4（+）T细胞系，其以HLA-DP 5限制性方式特异性响应于WT 1衍生肽WT 1（337-347）LSHLQMH-SRKH的刺激而增殖并产生Th 1细胞因子。NIK-1对HLA-DP 5阳性、表达WT 1的白血病细胞表现出细胞毒性，但不裂解HLA-DP 5阴性、表达WT 1的白血病细胞或HLA-DP 5阳性、WT 1阴性的细胞。NIK-1不抑制HLA-DP 5阳性个体的正常骨髓细胞的集落形成。这是第一个报告，描述了WT 1特异性和HLA II类限制性的CD 4（+）T淋巴细胞具有直接的细胞毒活性，对白血病细胞。
Wilms tumor gene 1 product (WT1) has been recognized as an attractive target antigen of immunotherapy for various malignancies including leukemia. Because tumor-associated antigen-specific CD4(+) T lymphocytes undoubtedly play an important role in the induction of an antitumor immune response, we attempted to generate WT1-specific CD4(+) T lymphocytes in vitro and examined their antileukemia functions. A CD4(+) T-cell line, designated NIK-1, which proliferated and produced Th1 cytokines specifically in response to stimulation with the WT1-derived peptide, WT1(337-347) LSHLQMH-SRKH, in an HLA-DP5-restriced manner was established. NIK-1 exhibited cytotoxicity against HLA-DP5-positive, WT1-expressing leukemia cells but did not lyse HLA-DP5-negative, WT1-expressing leukemia cells or HLA-DP5-positive, WT1-negative cells. NIK-1 did not inhibit colony formation by normal bone marrow cells of HLA-DP5-positive individuals. This is the first report to describe WT1-specific and HLA class II-restricted CD4(+) T lymphocytes possessing direct cytotoxic activity against leukemia cells.