CD40配体的基因转移可诱导慢性淋巴细胞白血病B细胞的自体免疫识别。
Gene transfer of CD40-ligand induces autologous immune recognition of chronic lymphocytic leukemia B cells.
作者信息
Kato K, Cantwell M J, Sharma S, Kipps T J
机构信息
Division of Hematology/Oncology, Department of Medicine and the UCSD Human Gene Therapy Program, UCSD School of Medicine, La Jolla, California 92093-0663, USA.
出版信息
J Clin Invest. 1998 Mar 1;101(5):1133-41. doi: 10.1172/JCI1472.
Abstract
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.
摘要
CD40与CD40配体（CD154）的相互作用在免疫激活中起关键作用。利用编码小鼠CD154的复制缺陷型腺病毒（Ad-CD154），我们对人慢性淋巴细胞白血病B细胞进行改造，使其表达功能性CD40配体。这不仅能诱导被感染细胞上免疫辅助分子的表达，还能使其反式激活未被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也会被下调。Ad-CD154感染的白血病细胞在混合淋巴细胞反应中是高效刺激物，能诱导产生针对自体未修饰白血病细胞的细胞毒性T淋巴细胞。因此，Ad-CD154可诱导宿主产生抗白血病反应，可能具有治疗潜力。
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