IgA肾病患者IL—2的产生及IL—2受体的表达

本文对IgA肾病(IgAN)外周血淋巴细胞白细胞介素2(IL-2)的产生、受体的表达及免疫球蛋白的产生进行了研究。结果发现:外周血淋巴细胞产生IL-2的活性明显增高,IL-2受体表达亦明显增强并伴有免疫球蛋白产生增多,提示IgAN存在着细胞免疫功能的紊乱。     

IL—10对外周血单个核细胞体外产生IL—2及IFN—γ的调节作用

为探讨Ｔｈ１与Ｔｈ２两类细胞因子间相互调节，研究了ｒｈＩＬ－１０对ＰＨＡ体外诱导人ＰＢＭＣ产生ＩＬ－２及ＩＦＮ－γ的影响。结果表明，１０ｎｇ／ｍｌＩＬ－１０明显抑制ＰＢＭＣ产生ＩＬ－２及ＩＦＮ－γ（Ｐ＜０．０２及Ｐ＜０．０１）。在加入兔抗人ＩＬ－１０抗体的ＰＢＭＣ体外培养体系中，在５μｇ／ｍｌ浓度时，ＩＬ－２产生可明显增加（Ｐ＜０．０５），随着抗体浓度增加，ＩＬ－２呈剂量依赖性增加（ｒ＝０．９６２，Ｐ＜０．０１），ＩＦＮ－γ产生亦增加，但差异不明显。本研究表明ＩＬ－１０抑制活化人ＰＢＭＣ体外产生ＩＬ－２及ＩＦＮ－γ，而抗人ＩＬ－１０抗体则表现出增强作用。ＩＬ－１０介导Ｔｈ１与Ｔｈ２两类辅助性Ｔ细胞间的相互调节，选择机体对抗原的免疫应答类型，从而对临床疾患的防治有一定指导意义。     

癌症患者外周血T淋巴细胞丝裂原反应性和血浆IL—2,IL—6活…

本文应用生物学测定法检测了肝癌，胃癌，大肠癌，喉癌、乳腺癌外周血Ｔ淋巴细胞丝裂原反应性和血浆ＩＬ－２，ＩＬ－６活性及ＩＬ－２受体的表达。     

IL_2,IL—4和IL—6对T细胞活化增殖的影响途径比较

单一的 PHA/PMA/OKT3不能诱导纯化的静止 T 细胞发生增殖反应,这为我们比较外加 IL—2/IL—4/IL—6对 T 细胞活化增殖的影响途径提供了条件.PHA 诱发了静止 T 细胞对 IL—2/IL—4/IL—6的增殖反应,而 anti—Tac 单抗只能抑制由 IL-2介导的增殖反应.PMA 能够诱导静止 T 细胞对 IL—2/IL—4发生增殖反应,而不对 IL—6发生增殖反应.OKT3单抗只能诱导静止 T 细胞对 IL—2发生增殖反应.免疫抑制剂环孢霉素 A(C_(?)A)均能抑制 PHA 联合 IL—2/IL—4/IL—6所诱发的 T 细胞增殖反应,但其抑制作用的动力学观察却得到三种完全不同形式的抑制结果.这些结果表明,这三种淋巴因子各有其独自的途径使T 细胞活化增殖.     

硒对LAK细胞活性的影响及其机理研究

研究了硒在体外对LAK细胞活性的影响及作用机理,结果证明在LAK细胞的诱导阶段加入10~5～10mol/L亚硒酸纳能增强LAK细胞的杀伤和增殖活性。采用流式细胞仪测Tac(IL—2Rα)表达,Slot-Blot检测硒对LAK细胞的IL—2RαmRNA水平的影响,结果表明硒能增强LAK细胞的Tac抗原表达和IL-2RαmRNA的水平,提示硒可能通过促进Tac的表达增强了LAK细胞对IL—2的敏感性,从而提高了LAK细胞的增殖及杀伤活性。因此硒可望作为一种新型的免疫调节剂用于抗肿瘤治疗。     

Interleukin 10 Inhibits TNF-Alpha Production in Human Monocytes Independently of Interleukin 12 and Interleukin 1 Beta

Previously we demonstrated that endogenously produced Interleukin (IL-)IO suppressed the production of tumor necrosis factor-alpha (TNF-alpha) in CD3 activated T-cells via downregulation of paracfine IL-12 secretion from APC. Here we investigated the effect of endogenous IL-10 on TNF-alpha production in purified lipopolysaccharide (LPS) stimulated monocytes and its mechanism. Similarly to its effects on T-cells, EL-10 inhibited monocyte TNF-alpha production by about half Unlike in T-cells, however, this effect was not mediated via IL-12. While blockade of endogenous IL-10 binding to the IL-10 receptor enhanced the autocrine production of TNF-alpha, IL-12 and IL-1 beta, the neutralization of IL-12 or IL-1 beta did not affect the EL-10 effects on TNF-alpha production. This suggests that despite its inhibitory effects on IL-12 and IL-1 beta, which is quite similarly observed in T-cells, in purified monocytes IL-10 does not effect its TNF-alpha suppression by this mechanism. These findings indicate that IL-10 regulates production of pro-inflammatory cytokines by distinct mechanisms in different cells and tissues. Our study thus adds to the appreciation of the complex cytokine regulation of the immune system.     

Interleukin 10 Inhibits TNF-Alpha Production in Human Monocytes Independently of Interleukin 12 and Interleukin 1 Beta

Previously we demonstrated that endogenously produced Interleukin (IL-)IO suppressed the production of tumor necrosis factor-alpha (TNF-alpha) in CD3 activated T-cells via downregulation of paracfine IL-12 secretion from APC. Here we investigated the effect of endogenous IL-10 on TNF-alpha production in purified lipopolysaccharide (LPS) stimulated monocytes and its mechanism. Similarly to its effects on T-cells, EL-10 inhibited monocyte TNF-alpha production by about half Unlike in T-cells, however, this effect was not mediated via IL-12. While blockade of endogenous IL-10 binding to the IL-10 receptor enhanced the autocrine production of TNF-alpha, IL-12 and IL-1 beta, the neutralization of IL-12 or IL-1 beta did not affect the EL-10 effects on TNF-alpha production. This suggests that despite its inhibitory effects on IL-12 and IL-1 beta, which is quite similarly observed in T-cells, in purified monocytes IL-10 does not effect its TNF-alpha suppression by this mechanism. These findings indicate that IL-10 regulates production of pro-inflammatory cytokines by distinct mechanisms in different cells and tissues. Our study thus adds to the appreciation of the complex cytokine regulation of the immune system.     

Modulation of the Interleukin 2 Receptor by Maternal and Cord Blood Serum

In this report, the potential inhibitive action, of maternal serum (retroplacental and peripheral), and cord blood serum on the expression of the I12r has been studied. Calf and male serum were used as a control. In order to have an optimal I12r expression, a previous PHA cellular stimulation was performed. the maternal serum's I12r inhibitive property was measured during and after the pregnant period. the presence of I12r on maternal lymphocytes, cord blood cells, and unrelated donor mononuclear cells has been investigated (after a PtfA stimulation assay). the down regulated Il2r expression of neoplastic cell line (Hut7g cell line) under the influence of maternal serum has been observed. the examination of the inhibitive action due to maternal serum has suggested that a factor included in the IgG fraction is mainly responsible for the down regulating property concerning the 112r expression. A possible mechanism for the action of this factor has been studied. Further experiments suggest that the addition of recombinant I12 during the action of low doses of maternal IqG allows a partial reexpression of the I12 receptor. However, at. physiological concentrations of IyC, thc Interleukin 2 receptor down regulation becomes Irreversible.     

Interleukin 2 therapy in severe atopic dermatitis

Interleukin 2 (IL-2) at a dose of 10,000 to 20,000 U/kg/q 8 hr was given for 9–12 days to six patients with cases of severe atopic dermatitis (AD) which were refractory to conventional therapy. After IL-2 therapy, the clinical symptoms and signs of eczema including pruritus, scratching, papulovesicles, and lichenification were much improved, but all of them recurred 2–6 weeks after stopping treatment. Adverse reactions were similar to those reported previously, but all of them subsided after discontinuation of therapy. Laboratory findings showed decreased T-cell subsets, especially CD4+ cells, and increased IL-2R+ (CD25) cells, but there was no significant change in serum IL-2, serum IgE, orin vitro IgE production. Immunopathological studies of the skin biopsies showed decreased mononuclear-cell infiltration, depletion of CD4+ cells, and enhanced expression of CD25 and HLA-DR antigens. As lymphokine-activated killer (LAK)-cell activity against cultured fibroblasts was similar in patients with AD and in normals and CD1+ Langerhans cells were not decreased after IL-2 therapy, we speculate that the depletion of helper/inducer CD4+ cells and hence abrogation of the exaggerated antigen processing and cellular activation in diseased skin are the explanation for the transient efficacy of IL-2 in the treatment of atopic dermatitis.     

Interleukin 2 induces a transient downregulation of protein phosphatase 1 and 2A activity in human T cells

Stimulation of human CD4* T cell lines with interleukin 2 (IL-2) induces tyrosine, serine and threonine phosphorylation of a series of proteins involved in the IL-2 receptor (IL-2R) signaling pathway. Here, we examined whether IL-2 induces changes in the activity of protein serine/threonine phosphatases in antigen specific, CD4* human T cell lines. Using inhibitors of protein phosphatases 1 (PP1), PP2A, and PP2B, we provide evidence, that IL-2 induces a downregulation of PP activity in the cytoplasmic/membrane fraction. Thus, IL-2R ligation for 30 min triggers a 16 percent decrease in total PP2A activity (p<0.00005, n =17) and a seven percent decrease in PP1 activity (p<0.00005, n =17). Cytokine-induced downregulation of PP2A activity reaches a maximum 60 min after IL-2R ligation, and returns to baseline levels within two hours. Downregulation of PP1 activity reaches a maximum after 30 min and is largely reversed one hour after IL-2 stimulation. As determined from immunoblotting experiments using a specific anti-PP1 or anti-PP2A antibody, the amount of PP1 and PP2A recovered from cytosolic/membrane fraction remains unchanged after IL-2 treatment suggesting that the drop in PP1/PP2A activity might be due to a regulatory change rather than to a change in the amount of PP1 and PP2A. In conclusion, we provide evidence, for the first time, that IL-2 induces a transient downregulation of PP2A activity in T cells. In addition, our findings indicate that cytoplasmic PPl activity is transiently downregulated following IL-2R ligation in antigen-specific, human CD4* T cells.     

Mechanisms of immunosuppression associated with severe nonthermal traumatic injuries in man: Production of interleukin 1 and 2

Depression of cell-mediated immunity in patients following severe traumatic injury has been well documentedin vitro andin vivo. However, the exact mechanism of this defect is still controversial. In this study, we have investigated the ability of injured patients' peripheral blood mononuclear cells (PBMC) to produce two important immunoregulatory molecules, interleukin 1 (IL 1) and interleukin 2 (IL 2). Eighteen traumatic injury patients were studied during the course of their hospital stay and their results compared with a group of 18 normal age- and sex-matched controls. The results showed the following. (1) Production of IL 2 by normal PBMC in response to optimal doses of mitogen may vary with sex as well as age. (2) Adherent mononuclear cells from trauma patients produced at least as much IL 1 as normals. (3) IL 2 production, however, was markedly suppressed (normals, 1.6 ± 0.2 U; traumatic injury, 0.6±0.1 U;P=0.001) and persisted for as long as 50 days postinjury. OKT4⁺ cells were not significantly decreased at any time, nor were OKT8⁺ suppressor/cytotoxic cells increased at any time. Decreased IL 2 production in patients treated with steroids or those who were septic was not different from that in those patients who were not treated with steroids or were not septic. These results suggest that the cause of the defect in IL 2 production in traumatic injury patients is not related to a lack of the IL 1 signal, producer T cells, or Ia⁺ monocytes or to increased suppressor T cells. However, it could be related to a lack of another macrophage signal to the T cell, another suppressor-cell population, or an active suppressor substance which has been identified in the serum of these patients.     

白介素-1受体相关激酶-2反义寡核苷酸对IL-1和TNF诱导PGI2合成的不同影响

目的研究白介素-1受体相关激酶-2(IRAK-2)反义寡核苷酸对白介素-1(IL-1)和肿瘤坏死因子(TNF)诱导前列腺环素(PGI2)合成的不同影响。方法白介素-1受体相关激酶-2反义寡核苷酸导入脐静脉内皮细胞以阻断白介素-1受体相关激酶-2的表达,用白介素-1及肿瘤坏死因子刺激细胞后,用竞争ELISA方法检测PGI2的合成。结果白介素-1受体相关激酶-2反义寡核苷酸可显著降低白介素-1诱导的PGI2合成,此效应强度存在时间和浓度依赖性,但白介素-1受体相关激酶-2反义寡核苷酸对肿瘤坏死因子诱导的PGI2合成无影响。结论白介素-1受体相关激酶-2反义寡核苷酸对IL-1和TNF诱导PGI2合成有不同影响。白介素-1受体相关激酶-2在IL-1诱导的PGI2合成中起重要作用。     

Influence of Bacterial Superantigen TSST-1 Against the Anti-Proliferative Efficacy of Immunosuppressive Drugs and Interleukin 2 Production in Peripheral Blood Mononuclear Cells of Hemodialysis Patients and Healthy Subjects

We investigated the influence of bacterial superantigen on the efficacies of immunosuppressive drugs on the blastogenesis of peripheral-blood mononuclear cells of 27 hemodialysis patients awaiting renal transplantation. The IC₅₀ values for prednisolone, methylprednisolone, cyclosporine, and tacrolimus evaluated in the superantigen-stimulated cells were significantly higher than those evaluated in concanavalin A-stimulated cells (p = 0.0002–0.018). Interleukin-2 amounts produced from superantigen-stimulated cells were significantly larger than those from concanavalin A-stimulated cells (p = 0.0363). These results suggest that superantigen attenuates the suppressive efficacies of glucocorticoids and calcineurin inhibitors by stimulating lymphocytes of hemodialysis patients awaiting transplantation to overproduce interleukin-2.     

人血单核细胞IL—1的制备与活性单位测定

本文报告应用人血白细胞血小板悬液和静脉血(3—5ml)54份,分离单核细胞用于产生IL-1。用小鼠胸腺细胞增殖法测定IL-1活性及滴定其活性单位。结果用人血白细胞血小板悬液制备的IL-1测定其单位平均为1265U/ml,此含IL-1的细胞培养上清液用于进一步提纯IL-1。54份血标本测定IL-1活性单位平均为64.12±113.5U/ml,计算其正常范围是0-291U/ml。应用免疫点迹法测定培养上清液中IL-1的特异性,结果测定样品与标准IL-1在硝酸纤维膜上均呈现同样的斑点,说明它们有共同的特异性。     

血小板活化因子对小鼠巨噬细胞受体结合及产生IL-1的探讨

本文探讨了血小板活化因子对硫乙醇酸钠刺激产生的小鼠腹腔巨噬细胞受体结合及产生白细胞介素1的状况。用PAF对~3H-PAF竞争结合实验,测定出对TG-Mφ膜结合的IC50,在20℃为8.5×10~(-9)M,0℃为9.7×10~(-9)M,两者无明显区别;而对TG-Mφ完整细胞的结合。在20℃为6.5×10~(-9)M,0℃为10.5×10~(-9)M,随温度的增高,IC50减小。NaCl有降低~3H-PAF特异结合的能力,IC50为7.5mM。PAF能够刺激TG-Mφ产生白细胞介素1,在10~(-3)M浓度较为明显,和对照组相比,P<0.05。