Linn Y C, Hui Kam M
Singapore General Hospital, Outram Road, Singapore and National Cancer Centre, Singapore.
Leuk Lymphoma. 2003 Sep;44(9):1457-62. doi: 10.3109/10428190309178764.
Cytokine-induced killer (CIK) cells are a unique population of cytotoxic T lymphocytes (CTL) with the characteristic CD3+CD56+ phenotype. These cells have demonstrated higher proliferative and cytolytic activities in comparison to the reported CD3-CD56+ lymphokine activated killer (LAK) cells that are essentially activated natural killer (NK) cells. CIK cells are non-MHC-restricted in target cell recognition and killing. We have shown the feasibility of generating CIK cells from a series of marrow samples of patients with acute myeloid leukemia (AML) collected at diagnosis. At maturity, the CIK cells exhibit potent cytotoxicity against autologous AML targets as well as allogeneic myeloid leukemia cells, regardless of the HLA types of these targets. This observed cytotoxicity is not entirely due to NK cells as prior pre-absorption of the NK cells cytolytic activities does not abolish the subsequent cytotolytic activities against leukemic targets. It has also been reported by others that CIK cells are cytolytic against chronic myeloid leukemia (CML) cells, both in vitro and in the SCID mouse tumor model. In a mouse transplant model across MHC barrier, the CIK cells generated from the donor do not induce graft vs. host disease as observed for unfractionated donor splenocytes. In comparison to untreated control mice, the infusion of CIK cells results in the prolonged survival of murine leukemia-bearing mice. CIK cells also express CD94, part of the NK receptor comprising of CD94-NKG2 heterodimer. However, only low level of the killer immunoglobulin-like receptors are expressed by the CIK cells. In addition, as reported for the classical CTL, CIK cells could interact with dendritic cells (DC) to result in the enhancement of cytotolytic activities against tumor cells. The characteristic biological properties of the CIK cells would, therefore, enable them to be exploited for anti-leukemic therapy.
细胞因子诱导的杀伤细胞（CIK细胞）是具有CD3 + CD56 + 表型特征的独特细胞毒性T淋巴细胞（CTL）群体。与报道的CD3 - CD56 + 淋巴因子激活的杀伤细胞（LAK细胞）相比，这些细胞表现出更高的增殖和细胞溶解活性，LAK细胞本质上是激活的自然杀伤（NK）细胞。CIK细胞在靶细胞识别和杀伤方面不受主要组织相容性复合体（MHC）限制。我们已经证明了从一系列急性髓系白血病（AML）患者诊断时采集的骨髓样本中生成CIK细胞的可行性。成熟时，CIK细胞对自体AML靶标以及异基因髓系白血病细胞表现出强大的细胞毒性，无论这些靶标的人类白细胞抗原（HLA）类型如何。观察到的这种细胞毒性并不完全归因于NK细胞，因为事先去除NK细胞的细胞溶解活性并不能消除随后对白血病靶标的细胞溶解活性。其他人也报道过，CIK细胞在体外和重症联合免疫缺陷（SCID）小鼠肿瘤模型中对慢性髓系白血病（CML）细胞具有细胞溶解作用。在跨越MHC屏障的小鼠移植模型中，供体产生的CIK细胞不会像未分离的供体脾细胞那样诱导移植物抗宿主病。与未处理的对照小鼠相比，输注CIK细胞可使荷鼠白血病小鼠的存活期延长。CIK细胞还表达CD94，它是由CD94 - NKG2异二聚体组成的NK受体的一部分。然而，CIK细胞仅表达低水平的杀伤免疫球蛋白样受体。此外，正如经典CTL的报道一样，CIK细胞可以与树突状细胞（DC）相互作用，从而增强对肿瘤细胞的细胞溶解活性。因此，CIK细胞的独特生物学特性使其能够用于抗白血病治疗。
