把这篇文章的摘要翻译了一下，由于水平有限，错误之处还请各位指正。 ) I/ Q5 E5 ?! l2 n& `$ qhymoglobulin, interferon-γ and interleukin-2 efficiently expand ^+ C9 y9 j' P( |) _
cytokine-induced killer (CIK) cells in clinical-grade cultures % ^; Q2 M8 u! D临床级培养中即复宁(兔抗人胸腺细胞免疫球蛋白)，干扰素γ和白细胞介素2有效扩增细胞因子诱导的杀伤细胞（CIK） ( X% W1 ]- G/ z' ~2 fJournal of Translational Medicine 2010, 8:129 " k! Z! a7 }1 M( x' a% m% W$ b: q0 c/ `+ }转化医学，2010,8:129 & D( p; a _; A. cABSTRACT- u0 S4 ^8 g, U. _, a, i
Background. Cytokine-induced killer (CIK) cells are typically differentiated in vitro with interferon (IFN)-γ and αCD3 monoclonal antibodies (mAb), followed by the repeated provision of interleukin (IL)-2. It is presently unknown whether thymoglobulin (TG), a preparation of polyclonal rabbit γ immunoglobulins directed against human thymocytes, can improve the generation efficiency of CIK cells compared with αCD3 mAb in a clinical-grade culture protocol.* _" B6 @4 _# B6 B% J
背景：细胞因子诱导的杀伤细胞（CIK）是在体外应用γ干扰素（IFN-γ）、αCD3单抗（mAb），白细胞介素2（IL-2）、刺激诱导分化的一类细胞。目前未知是否一种由多克隆兔γ免疫球蛋白制备的兔抗人胸腺细胞免疫球蛋白（TG）可以直接对抗人胸腺细胞，在临床级细胞培养方案中是否能与αCD3单抗（mAb）配合一起促进CIK细胞的增殖效率。8 |# l% h& d) a$ X8 G4 V0 j
Methods. Peripheral blood mononuclear cells (PBMC) from 10 healthy donors and 4 patients with solid cancer were primed with IFN-γ on day 0 and low (50ng/ml), intermediate (250 ng/ml) and high (500 ng/ml) concentrations of either αCD3mAb or TG on day 1, and were fed with IL-2 every 3 days for 21 days. Aliquots of cells were harvested weekly to monitor the expression of representative members of the killer-like immunoglobulin receptor (KIR), NK inhibitory receptor, NK activating receptor and NK triggering receptor families. We also quantified the frequency of / T- c4 }5 C/ y( w& ?' s: J0 vbona fide regulatory T cells (Treg), a T-cell subset implicated in the down-regulation of anti-tumor immunity, and tested the in vitro cytotoxic activity of CIK cells against NK-sensitive, chronic myeloid leukaemia K562 cells. ' u& X$ s' \" N w+ C; }方法：从10个健康者和4个实体瘤患者中采集外周血单个核细胞（PBMC），第0天首先经IFN-γ处理，第1天分别添加低浓度（50 ng/ml），中浓度(250 ng/ml)和高浓度(500 ng/ml) 的αCD3 mAb或TG，每3天添加1次IL-2，总共21天。每周收集部分细胞检测其杀伤细胞免疫球蛋白样受体（KIR），NK抑制受体，NK活化受体和NK触发受体家族。同时鉴定调节性T细胞（一种抑制抗瘤免疫反应的T细胞亚群）的数量，以及检测体外CIK细胞的自然杀伤活性，对慢性骨髓性白血病K562细胞的杀伤活性。2 t9 f: @, G8 t
Results. CIK cells expanded more vigorously in cultures supplemented with intermediate and high concentrations of TG compared with 50 ng/ml αCD3 mAb. TG-driven CIK cells expressed a constellation of NK activating/inhibitory receptors, such as CD158a and CD158b, NKp46, NKG2D and NKG2A/CD94, released high quantities of IL-12p40 and efficiently lysed K562 target cells. Of interest, the frequency of Treg cells was lower at any time-point compared with PBMC cultures$ d0 D( z+ l: {/ z1 W
nurtured with αCD3 mAb. Cancer patient-derived CIK cells were also expanded after priming with TG, but they expressed lower levels of the NKp46 triggering receptor and NKG2D activating receptor, thus manifesting a reduced ability to lyse K562 cells., M! g0 s, s* v6 G& s9 O
结果：与浓度为50 ng/ml 的αCD3 单抗相比，添加中浓度及高浓度的TG更能有效扩增CIK细胞有。TG诱导的CIK细胞表达NK活化/抑制性受体，如CD158a和CD158b，NKp46，NKG2D及NKG2A/CD94，释放大量的白细胞介素-12p40，有效溶解K562靶细胞。有趣的是，TG诱导的外周血单个核细胞与αCD3 mAb诱导的外周血单个核细胞相比，调节性T细胞的检出率比任何时候都要低。癌症患者衍生出来的CIK细胞在TG作用下同样能够进行培养扩增，但此时CIK细胞只表达很低水平的NKp46触发受体和NKG2D活化受体，这就意味着溶解K562细胞的能力下降。 0 L0 A( P$ W* X' d1 kConclusions. TG fosters the generation of functional CIK cells with no concomitant expansion of tumor-suppressive Treg cells. The culture conditions described herein should be applicable to cancer-bearing individuals, although the differentiation of fully functional CIK cells may be hindered in patients with advanced malignancies.9 R) `/ B) j! x6 z
结论：TG可以促进功能CIK细胞的增殖，并没有伴随肿瘤免疫抑制作用的调节性T细胞的增殖。虽然全功能CIK细胞的分化也许会对晚期恶性肿瘤患者有所影响，但以本研究的培养条件诱导扩增的CIK细胞仅适用于个别荷瘤患者，。 1 D8 k( b+ W% x6 e, x作者: ckaixuyan 时间: 2012-7-16 14:17