Parajuli P, Nishioka Y, Nishimura N, Singh S M, Hanibuchi M, Nokihara H, Yanagawa H, Sone S
Third Department of Internal Medicine, University of Tokushima School of Medicine, Japan.
J Leukoc Biol. 1999 Jun;65(6):764-70. doi: 10.1002/jlb.65.6.764.
Dendritic cells (DC) play a key role in the initiation of immune response by stimulating the naive T cells. The fate of DC after the initiation of immune response is not clearly understood. Although there are few reports implicating natural killer (NK) cells in the elimination of DC, killing of DC by LAK cells, and specifically by T cells, has not been studied. In this study, we observed that DC, generated from monocytes, in vitro in the presence of granulocyte-macrophage colony-stimulating factor, interleukin-4 (IL-4), and tumor necrosis factor alpha were susceptible to cytolysis by lymphokine-activated killer (LAK) cells induced in the presence of IL-2 and IL-15 but not IL-12 alone. However, LAK cells induced by a combination of IL-12 and suboptimal dose of IL-2 were cytotoxic to DC. When purified lymphocytes were activated with IL-2, the CD8+/CD57- fraction (T-LAK), but not the CD8-/CD57+ fraction (NK-LAK) was cytotoxic to autologous DC. However, when unseparated peripheral blood mononuclear cells were used to generate LAK cells, both T-LAK and NK-LAK fractions showed equal cytotoxicity against autologous DC. Monoclonal antibodies against CD54, CD11a, and CD18 significantly inhibited the cytolysis, indicating that the killing involves the engagement of CD54 with its ligands.
树突状细胞（DC）通过刺激初始T细胞在免疫反应的启动中发挥关键作用。免疫反应启动后DC的命运尚不清楚。尽管有少数报道表明自然杀伤（NK）细胞参与DC的清除，但淋巴因子激活的杀伤细胞（LAK细胞），特别是T细胞对DC的杀伤作用尚未得到研究。在本研究中，我们观察到在粒细胞-巨噬细胞集落刺激因子、白细胞介素-4（IL-4）和肿瘤坏死因子α存在的情况下，由单核细胞体外产生的DC易被在IL-2和IL-15存在下诱导产生的LAK细胞溶解，但单独的IL-12不能诱导。然而，由IL-12和次优剂量的IL-2联合诱导产生的LAK细胞对DC具有细胞毒性。当用IL-2激活纯化的淋巴细胞时，CD8+/CD57-亚群（T-LAK）对自体DC具有细胞毒性，而CD8-/CD57+亚群（NK-LAK）则没有。然而，当使用未分离的外周血单个核细胞产生LAK细胞时，T-LAK和NK-LAK亚群对自体DC均表现出同等的细胞毒性。抗CD54、CD11a和CD18的单克隆抗体显著抑制细胞溶解，表明这种杀伤作用涉及CD54与其配体的结合。
