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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。
2 \* _6 {. a& l2 p7 r& T. J7 \hymoglobulin, interferon-γ and interleukin-2 efficiently expand) A, A: V- o2 Y& c; g4 x
cytokine-induced killer (CIK) cells in clinical-grade cultures
, x( r- B- D3 o" P+ h+ `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）
" w. H' K" u9 w8 _& ?Journal of Translational Medicine 2010, 8:129$ A: ?. n! l4 ~6 _
转化医学，2010,8:129& C* x+ r* Z( h0 y# D
ABSTRACT: m7 s M! ~& C- [- F) i3 p4 A/ R" T
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.
0 I8 Y* W. U/ K8 M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。
4 ?9 b- m: J* Y3 \3 g" iMethods. 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- `- Z/ Y8 y& X* ~3 M
bona 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./ k+ Z' v2 `+ O+ i$ m& g$ T
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。
) C2 _! Z! ~1 d4 CResults. 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
3 \, m$ K: V( Z4 j; cnurtured 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.
) I8 u9 d, c: W1 ~2 F2 o" I8 j/ }3 n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。1 O* ?' x( v" J+ l% {2 q+ o
Conclusions. 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.2 o" h; o9 p4 x. z3 g$ y! F5 v C9 \7 R
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，。
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发表于 2010-12-9 11:15
发表于 2011-5-5 09:33
