Gene transfer of CD40-ligand induces autologous immune recognition of chronic lymphocytic leukemia B cells
Gene transfer of CD40-ligand induces autologous immune recognition of chronic lymphocytic leukemia B cells
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DOI：
10.1172/jci1472
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发表时间：
1998-03-01
影响因子：
15.9
通讯作者：
Kipps, TJ
中科院分区：
文献类型：
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作者：
Kato, K;Cantwell, MJ;Kipps, TJ
CD 40-CD 154（CD 40-ligand，CD 154）相互作用在免疫激活中起着重要作用。我们用编码小鼠CD 154的复制缺陷型腺病毒（Ad-CD 154）修饰人慢性淋巴细胞白血病B细胞，使其表达CD 40的功能性配体。这不仅诱导感染细胞上免疫辅助分子的表达，而且使其能够反式激活未感染的旁观者白血病B细胞。此外，削弱白血病B细胞抗原呈递能力的因子被下调。Ad-CD 154感染的白血病细胞在混合淋巴细胞反应中是非常有效的刺激物，并且可以诱导产生对自体未修饰的白血病细胞特异性的细胞毒性T淋巴细胞，因此，Ad-CD 154可以诱导可能具有治疗潜力的宿主抗白血病应答。
CD40-CD40-ligand (CD154) interactions play a critical role in immune activation, Using replication defective adenovirus encoding mouse CD154 (Ad-CD154), we modified human chronic lymphocytic leukemia B cells to express a functional ligand for CD40. This not only induces expression of immune accessory molecules on the infected cell, but also allows it to trans-activate noninfected bystander leukemia B cells, Also, factors that impair the antigen-presenting capacity of leukemia B cells are downmodulated. Ad-CD154-infected leukemia cells are highly effective stimulators in mixed lymphocyte reactions and can induce generation of cytotoxic T lymphocytes specific for autologous nonmodified leukemia cells, As such, Ad-CD154 can induce a host antileukemia response that may have therapeutic potential.