淋巴因子对人PBMNC的LAK细胞形成、增殖和细胞毒作用的影响

应用乳酸脱氢酶释放法对重组白介素２，粗制天然白介素２，重组肿瘤坏死因子和天然免疫活性肽等淋巴因子诱导人ＰＢＭＮＣ为ＬＡＫ细胞以及ＬＡＫ细胞对靶细胞（人外周血淋巴细胞，人食管癌１０９细胞株和人红白血病细胞株＿（５６２）的细胞毒作用分别于培养的第４ｄ和第７ｄ进行了检测。结果显示：①四个配伍组和一个重组白介素２组的多克隆ＬＡＫ细胞攻击溶解１０９细胞株和Ｋ＿（５６２）细胞株的水平波动子２８％和６６％之间，中位数为４７％，而对正常人外周血淋巴细胞均无细胞毒作用；②重组白介素２和粗制天然白介素２配伍培养ＬＡＫ细胞的增殖协力约高于重组白介素２和重组肿瘤坏死因子组，以及重组白介素２和免疫活性肽组增殖协力的３倍，③在诱导ＬＡＫ细胞的过程中其增殖量和其细胞毒活性可以不同步。建议临床上治疗晚期肿瘤病人除用ＬＡＫ细胞和重组白介素２外，首先选用天然白介素２。     

单克隆抗体对活化腹腔巨噬细胞抗胰腺癌作用的影响

观察重组人白细胞介素２（γ－ＩＬ２）体外诱导的腹腔巨噬细胞，在ＹＰＣ３抗人胰腺癌单克隆抗体（ＹＰＣ３ｍＡｂ）介导下，通过抗体依赖性细胞介导的细胞毒性（ＡＤＣＣ）机制对胰腺癌细胞的杀伤作用。４ｈ５１Ｃｒ释放实验表明，在ＹＰＣ３ｍＡｂ作用下，活化腹腔巨噬细胞对Ｃａｐａｎ－２人胰腺癌细胞的杀伤活力明显增强，比单用巨噬细胞杀伤活力约提高７０．０％，而对照１－Ｆ／７抗登革热病毒单抗无明显影响。γ－ＩＬ２作用的腹腔巨噬细胞和脾淋巴细胞具有类似的ＡＤＣＣ杀伤效应。结果提示，γ－ＩＬ２和ＹＰＣ３ｍＡｂ联合腹腔注射，可能为胰腺癌的局部治疗提供一个新方法。     

Role of Interleukin-2 Activated MHC-Nonrestricted Lymphocytes in Antileukemia Activity and Therapy

Although the application of biological therapy for solid tumors with cytokines and adoptively transferred activated lymphocytes has received substantial attention, this approach has not been actively explored in treatment of hematopoietic neoplasms. This review will address the possibilities of interleukin-2 (IL-2) and IL-2 activated natural killer (NK) cells and T cells in antileukemia reactivity and therapy. The new approaches to optimal activation and generation of oncolytic cells, selective propagation of lymphocyte subsets, and the role of adhesion molecules in antileukemia cytotoxicity will also be addressed. We trust that this article will be conducive to the development of new directions in leukemia research and treatment.     

Studies of the influence of immunological and serological factors from patients with cholestasis due to alcoholic or viral hepatitis on biliary function in the rat

Abstract. Studies were undertaken to (a) determine if cholestasis in alcoholic or viral hepatitis is related to immunologic hyperreactivity as suggested for cholestasis due to type-II drug-induced hepatitis, and (b) evaluate possible mechanisms involved in lymphokine-induced cholestasis. Results indicate that a cholestatic factor exists in alcoholic and acute viral hepatitis. Supernatants of lymphocytes from patients with alcoholic hepatitis stimulated by an extract of alcoholic hyalin evoked a 28%pL7·3 SEM reduction in rat bile flow ( P <0·03). Supernatants of lymphocytes from patients with acute viral hepatitis activated by liver-specific protein caused a reduction in rat bile flow of 24%pL5·9 SEM ( P <0·03). A decrease in bile flow also occurred following injections of sera from patients with alcoholic or acute viral hepatitis. In contrast, injection of supernatants of non-stimulated lymphocytes or those from chronic active hepatitis or healthy subjects did not produce a significant change in bile flow. Supernatants of stimulated lymphocytes from tuberculin-sensitized guinea pigs caused a similar decrease in rat bile flow and reduced excretion of human secretory immunoglobulin A (IgA). Despite reductions in rat bile flow there were no alterations in liver morphology, liver plasma membrane Na-K-ATPase activity, microsomal cholesterol-7 α -hydroxylase activity or low-dose indocyanine green clearance during the period of observation.     

淋巴因子激活的杀伤细胞与自发性高血压大鼠的一氧化氮样内皮依赖性舒血管因子

目的探讨淋巴因子激活的杀伤细胞（ＬＡＫ细胞）与一氧化氮样内皮依赖性舒血管因子（ＥＤＲＦ）作用的相关性。方法动态观察自发性高血压大鼠（ＳＨＲ，ｎ＝５）ＬＡＫ细胞的增殖、活性及其所表达的ＳＯＤ样物质活性当量、自由基清除效应。同时观察胸主动脉环对乙酰胆碱（Ａｃｈ）的舒张反应，以及上述ＬＡＫ细胞与ＳＯＤ标准品对主动脉环（ｎ＝３０）的Ａｃｈ舒张反应的影响，与等量ＷＫＹ大鼠比较。结果与ＷＫＹ比，ＳＨＲ的ＬＡＫ细胞增殖、活性及其所表达的ＳＯＤ样物质和其自由基清除效应均明显降低（Ｐ＜０．０５），经ＬＡＫ细胞（无论来自ＷＫＹ还是ＳＨＲ）孵育后的主动脉环对Ａｃｈ的舒张反应均有不同程度增加。标准ＳＯＤ与ＬＡＫ细胞有相同效应。结论ＬＡＫ细胞可能通过表达ＳＯＤ样物质来减少ＮＯ氧化分解从而增强主动脉环的ＮＯ样舒血管作用。     

Complete remission of recurrent glioblastoma multiforme following local infusions of lymphokine activated killer cells

Summary We report the case of a 26-year-old man in whom glioblastoma multiforme had recurred six months following a subtotal resection. Despite radiotherapy and a course of interferon beta and ACNU, the tumour increased in size (to 3 cm) and there was neurological deterioration. Treatment was then initiated with LAK cells, together with ACNU and interferon beta. After three courses of LAK cells, tumour size was markedly reduced, and at about six months the tumour had nearly disappeared on computed tomographic (CT) scans. At one year, and after nine courses of LAK cell therapy (total dose of 2.7×10⁹ cells) infused via an Ommaya reservoir and supplemented by ACNU and interferon beta, the tumour has disappeared and the patient is considered to be in complete remission since 6 months. This marked response is thought to be due chiefly to LAK cell therapy. The relatively low dose administered was well-tolerated.     

Human interleukin-2 activated cytotoxic cells kill autologous glioma cells in vitro

Summary We have cultured peripheral blood lymphocytes (PBL) from glioblastoma patients in recombinant interleukin-2 (IL-2) containing medium for a period of 5 days. The cytotoxicity of these cells was tested on ⁵¹Cr-labelled autologous dissociated glioblastoma cells which had not been cultured. Significant cytotoxicity against glioma cells was observed in seven out of nine cases. IL-2 activated PBL from normal donors were equally cytotoxic against these glioma cells. Autologous lymphocytes activated by phytohaemagglutinin were also lysed in most cases, and the erythroleukemia cell line K562 was highly susceptible to the cytotoxic capability of the IL-2 activated PBL. In cold target inhibition experiments, K562 inhibited the cytotoxicity against both autologous and allogenic glioma cells, and glioma cells inhibited the cytotoxicity against K562. Following immunomagnetic separation, the IL2 activated cells demonstrated cytotoxicity against glioma cells, K562 cells, and PHA blasts in both the CD8⁺ and the CD8^– subsets.     

人骨转移瘤肿瘤浸润淋巴细胞的过继免疫治疗

肿瘤浸润淋巴细胞(TIL)的杀伤肿瘤细胞效应比淋巴因子活化杀伤细胞(LAK)更为有效低毒。作者用手术与活检的方法从骨转移瘤标本中分离TIL,经体外重组白细胞介素—2(rIL—2)激活并扩增,过继转输10例骨转移瘤病例,完全应答1例,部分应答2例,弱应答3例,无应答4例。有效应答30%。     

The effects of interleukin 2 on early and late thymocyte differentiation in foetal thymus organ culture

The effects of interleukin 2 (IL-2) on in vitro T cell development in organ cultures of day 14 foetal mouse thymus were investigated. Over a 12 day culture period IL-2 was found to inhibit the development of each of the major thymocyte subpopulations, defined by CD4 and CD8 expression. Since each subpopulation was reduced in number, a common precursor to these subsets was thought to be inhibited by IL-2. Indeed, subsequent analyses of subsets of CD4- CD8- cells, characterized by expression of HSA, Pgp-1, and IL-2R, demonstrated that CD4- CD8- cells expressing IL-2R and their postulated progeny were reduced in IL-2-treated cultures. The number of cells reputed to be the immediate precursor of CD4- CD8- IL-2R+ cells, i.e. CD4- CD8- Pgp-1+IL-3R- cells, was not change by treatment with IL-2. Interestingly, however, numbers of the most immature subset of CD4- CD8- cells, identified as having the HSA1oPgp-1+IL-2R- and CD3- phenotype, increased in IL-2-treated cultures and was the only population of cells to do so. We also document the failure to detect any LAK cell activity against syngeneic thymocytes in IL-2-treated cultures and therefore hypothesize that the inhibition of T cell differentiation in these cultures is due to an arrest in differentiation of CD4- CD8- cells bearing the IL-2R.