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1.
To explore the expression of Beclin1 in osteosarcoma and investigate the effects of down-regulation of autophagy on the chemotherapeutic sensitivity to cisplatin (DDP), the expression of Beclin1 in 28 specimens of osteosarcoma (group A) and 19 specimens of normal bone tissues (group B) were immunohistochemically detected. The expression of Beclin1 mRNA in MG63 cells treated with different concentrations of DDP was examined with RT-PCR. After down-regulation of autophagy in MG63 cells by an autophagy inhibitor, 3-methyladenine (3-MA), the cell proliferation inhibition rate of MG63 cells treated with DDP was evaluated by using the MTT assay. The positive rates of Beclin1 were 67.85% in group A and 94.73% in group B. Its expression was lower in osteosarcoma than in normal bone tissues, with a significant difference found between them (P〈0.05). RT-PCR showed that the expression of Beclin1 mRNA in the cells treated with high-dose DDP were higher than that in the non-treated cells, and no significant difference in the expression of Beclin1 mRNA was found between the cells treated with low-dose DDP and the non-treated cells. There was a positive correlation between the level of Beclin1 mRNA expression and the concentration of DDP. MTT assay showed that the proliferation inhibition rates of the cell treated with 3-MA and DDP combined were substantially increased when compared with those treated with DDP alone (P〈0.01). This study demonstrated that autophagy may be implicated in the carcinogenesis of osteosarcoma, and DDP may induce autophagy in the MG63 cells. It also suggests that the down-regulated autophagy could increase chemotherapeutic sensitivity of DDP to osteosarcoma.  相似文献   

2.
Dr Margaret Chan takes office as WHO Director-General   总被引:4,自引:0,他引:4  
Background The aim of the current study was to investigate the role of interleukin (IL)-2, interferon (IFN)-y, IL-4 and IL-10 in a concordant hamster-to-rat cardiac xenotransplantation model. Methods A hamster-to-rat cardiac transplantation was performed using SD rats as recipients of Golden Syrian hamster hearts. A total of 60 SD rats were divided into four groups and treated as follows: control group (n=15); splenectomy group (n=15); CsA group (n=15); CsA + splenectomy group (n=-15). Levels of IL-2, IFN-γ, IL-4 and IL-10 were measured by enzyme linked immunosorbent assay (ELISA). Sera were harvested at different time points in each group: day 1, and 3 as well as the day the xenograft stopped beating in the control group and CsA group; day 1, 3, 7, 14 and 30 in the splenectomy group and CsA+splenectomy group. The expression of P-selectin and intercellular adhesion molecule-1 (ICAM-1) was examined by immunohistochemical analysis of the xenogralt alter cardiac xenotransplantation. Results Serum levels of IL-2 and IFN-γ were upregulated in untreated (day 3) and splenectomy-treated animals (day 7) compared to CsA + splenectomy treated animals (day 7). IL-10 was upregulated in long-term survival recipients following splenectomy + CsA. Neither P-selectin nor ICAM-1 expression was detected in long-term survival xenografts. Conclusions Serum IL-2 and IFN-γ were elevated following acute vascular rejection. Serum IL-10 was correlated to immunosuppression and protective effects in long-term survival rats following concordant cardiac xenotransplantation.  相似文献   

3.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer agent. Epigallocatechin-3-gallate (EGCG) is a polyphenolic constituent of green tea. In this study, inhibitory effect of combined use of EGCG and TRAIL on human melanoma A375 cells was examined and the possible mechanism investigated. The cells were divided into 4 groups: control group, EGCG group (EGCG: 10, 20 μg/mL), TRAIL group (TRAIL: 25 ng/mL) and EGCG+TRAIL group (combined group). The growth inhibition was measured in the A375 cells treated with different concentrations of TRAIL ((25, 50, 75, 100, 125, 150 ng/mL) by MTT assay. The apoptosis was assessed by flow cytometry. The expressions of DR4 and DR5 were detected by flow cytometry and western blotting. The activities of caspase-8 and caspase-3 were determined by colorimetric assay. The results showed that TRAIL could dose-dependently inhibit the growth of A375 cells and the IC50 of TRAIL was 150 ng/mL. The apoptosis rate was 11.8% in the TRAIL group, 5%–7% in the EGCG group and 48.9%–59.1% in the combined group. Significant difference was found in the apoptosis rate between the combined group and the EGCG or TRAIL group (P〈0.05 for each). The expression of DR4 instead of DR5 was significantly increased in the EGCG group. The activity of caspase-3 rather than caspase-8 was substantially enhanced in the EGCG group. These results suggest that EGCG is useful for the TRAIL-based treatment for melanoma.  相似文献   

4.
Objective:To investigate the effects and mechanisms of interferon in combination with alltrans retinoic acid (ATRA) on proliferation and differentiation of ATRA-resistent APL cell. Methods :After MR2 cells (ATRA-resistance cell line) were treated with IFN-α, IFN-γ and ATRA alone or IFN-α and IFN-γ in combination with ATRA respectively. The cell proliferation was tested by MTT test and the cell differentiation was tested through light microscope by NBT test and flow cytometry (FCM). The expres sion of promyelocytic leukemia (PML) protein was observed by indirect immune fluorescent method. Results: Both IFN-α and IFN-γ could inhibit the proliferation and induce the differentiation of MR2 cells to some extent. The effects were more obvious after both interferons in combination with ATRA respectively (P〈0.05). Moreover, the maturation of MR2 cells induced by IFN-γ+ATRA group was more higher than that by IFN-α+ATRA group (P〈0. 05). Both interferons could induce the expressions of PML protein. Conclusion:Both interferons can inhibit MR2 cells proliferation, which may be related to the expression of PML protein induced by both interferons. The inducing differentiation effects of IFN-γ+ATRA group on MR2 cells are more powerful than those of IFN-aq-ATRA group, which may be related to the different signal transduction pathway of both interferons.  相似文献   

5.
Objective To investigate the role of T cell and its subsets in the induction of insulifis and type 1 diabetes mellitus (T1DM) in BALB/c mice. Methods Autoimmune diabetes mellitus was developed by intraperitoneal injection of 40 mg/kg streptozotocin (STZ) daily for 5 consecutive days in BALB/c mice as sources of donor cells. Spleen cells from diabetic mice were then cultured for 7 days in the stimulation of interleukin-2 (IL-2) to harvest diabetogenic T cells, which were subse-quently transferred into normal BALB/c mice recipients. MTT, ELISA, and HE staining were used to analyze the lym- phocyte proliferation, cytokine ( IL-2, interferon-γ, IL-4, and IL-10) levels, and pathological changes in pancreatic is- lets. Results As few as 3×10^6 diabetogenic T cells successfully induced diabetes mellitus in recipients pretreated with STZ twice, whereas transfer of equal amount of normal splenocytes, T cell-depleted diabetogenic splenocytes, or diabe-togenic CD4^+ T cells alone in recipients receiving STZ twice pretreatment was proved not to induce diabetes mellitus either. A markedly increased lymphocyte proliferation, high levels of interferon-γ/and IL-2 in the supernatants of diabeto-genic T cells were observed. In addition, a markedly enhanced lymphocyte proliferation, a high level of interferon-γ/secretion in serum, and numerous lymphocytes infiltration in pancreatic islets were detected in the diabetic mice induced by diabetogenic T cells transfer. Conclusions A novel T1DM murine model is established in STZ-pretreated BALB/c mice by adoptive transfer of diabetogenic T cells. CD4^+ T cells with interferon-γ/may promote the onset of diabetes mellitus.  相似文献   

6.
Background Vitamin D3 and its metabolites have been found to exert immunosuppressive effects both in vivo and in vitro. We investigated the synergistic effect of calcitriol and cyclosporine A (CsA) on lymphocyte proliferation in vitro and graft rejection following rat liver allotransplantations in vivo.Methods Alloantigen driven, human peripheral mononuclear cells’ proliferation and cytokine production capacity were tested in the presence or absence of various concentrations of calcitriol or CsA. In vivo, liver allografts were transplanted in a high responder strain combination (SD to Wistar) rats and combination of subtherapeutical dose of CsA and calcitriol was administered in recipients, whereas the control recipients received single or no immunosuppressant. Proliferation of splenocyte from recipient was tested with mixed lymphocyte reaction. Serum interleukin-2 (IL-2) and interferon gamma (IFN-γ) concentrations were measured with enzyme linked immunosorbent assay. Results Combined medication of 10(-9) mol/L calcitriol and 100 ng/ml CsA inhibited human peripheral mononuclear cells’ proliferation to alloantigen and the production of IL-2 and IFN-γ but promoted that of IL-4 and IL-10. Similarly, combination of 250 ng·kg(-1)·d(-1) calcitriol and 1.0 mg·kg(-1)·d(-1) CsA showed an additive effect in liver transplant model. It restrained splenocyte proliferation to alloantigen from donor and significantly reduced serum concentration of IL-2 and IFN-γ in recipients. Consequently, allograft rejection in combined medication group was minor (median William’s grade was 1.0 vs 3.0 in combined medication group and in the control group, P<0.05) and the recipients’ survival was evidently prolonged [(93.7±5.8) days vs (12.6±1.4) days in combined medication group and in the control group, P<0.01].Conclusion A combination of calcitriol and CsA has an additive effect on limiting lymphocyte proliferation and prolonging liver graft survival. With its additional immunomodulating property, calcitriol is a potent immunosuppressant that can extend the therapeutic window of classical immunomodulators in prevention and treatment of liver graft rejection.  相似文献   

7.
To investigate the effect of the Ginkgo Biloba Extract (GBE) on the asthma and examine its possible mechanisms, 75 asthma patients were divided into 4 groups and the patients were respectively treated with fluticasone propionate for 2 weeks or 4 weeks, or treated with fluticasone propionate plus GBE for 2 weeks or 4 weeks. Fifteen healthy volunteers served as healthy controls. Sputum inhalation with inhaling hypertonic saline (4%-5%) was performed. Lung ventilatory function and forced expiratory volume in one second (FEVI) were measured. The numbers of different cells in induced sputum were calculated. The expression of PKCα in the cells was immunocytochemically detected and the percentages of positive cells in different cells were counted. Interleukin-5 (IL-5) in sputum supernatants was detected with enzyme-linked immunosorbent assay. The percentage of eosinophils, lymphocytes, PKCα positive inflammatory cells and the concentration of IL-5 in asthmatic patients were higher than those in the controls (P〈0.05), and the eosinophils, lymphocytes, positive expression of PKCα and the level of IL-5 were significantly decreased in asthmatic patients after they were treated with fluticasone propionate or fluticasone propionate plus GBE. However, they were still significantly higher than those of the controls. Compared to the group treated with glucocorticosteroid for 2 weeks, no significant decrease was found in the percentage of eosinophils, lymphocytes, PKCα positive inflammatory cells and the IL-5 in the supernatant of induced sputum. Compared with the group treated with glucocorticosteroid for 2 or 4 weeks, significant decrease in the same parameters was observed in the group treated with fluticasone propionate and GBE for 4 weeks. The IL-5 level in the supernatant of induced sputum was positively correlated with the percentage of PKCα-positive inflammatory cells and the percentage of eosinophils in the induced sputum in asthma patient groups respectively (n=150, r=0.83, P〈0.01; n=150,  相似文献   

8.
The function of CD4+CD25+ regulatory T lymphocytes (Treg) in patients with acute coronary syndrome (ACS) and the effects of atorvastatin were investigated. Forty-eight patients with ACS were randomly divided into two groups: group C receiving conventional therapy (n=24), and group C+A receiving conventional therapy+atorvastatin (10 mg/day, n=24). T lymphocytes from ACS patients (before and 2 weeks after the treatment) or 18 healthy subjects were separated and the flow cytometry was used to measure the percentage of Treg. The inhibitory ability of Treg on effector T cells was determined by mixed lymphocyte reaction (MLR). ELISA was used to measure the serum levels of cytokines (IL-10, TGF-β1 and IFN-γ) before and after treatment. The results showed that as compared with normal control group, Treg percentage was decreased significantly (P〈0.01), the inhibitory ability of Treg on the T lymphocytes proliferation was reduced (P〈0.01), IFN-γ levels were increased and IL-10 and TGF-β1 levels were lowered in ACS patients. After treatment with atorvastatin, Treg percentage and the inhibitory ability of Treg on T lymphocytes proliferation were significantly increased in ACS patients. Serum IFN-γ was decreased significantly, while IL-10 and TGF-β1 were elevated significantly as compared with the non-atorvastatin group. The number of Treg was positively correlated with serum TGF-β1, but negatively with serum IFN-γ and CRP. It was concluded that ACS was associated with decreased number and defected function of Treg, which may play an important role in initiating immune-inflammatory response in ACS. The inhibitory effects of atorvastatin on inflammation in ACS may be due to its beneficial effects on Treg and restoration of immune homeostasis.  相似文献   

9.
Objective: To investigate the effects of sodium copper chlorophyllin (SCC) on the proliferation, differentiation and immunomodulatory function of mesenchymal stem cells (MSCs) from mice with aplastic anemia. Methods: A mouse model of aplastic anemia was established by exposure of BALB/c mice to sublethal doses of 5.0 Gy Co60 γ radiation, followed by transplantation of 2×1000000 lymph node cells from DBA/2 donor mice within 4 h after radiation. Aplastic anemic BALB/c mice were randomly divided into six groups: the treated groups, which received 25, 50, or 100 mg/kg/day SCC, respectively; a positive control group treated with cyclosporine A (CsA); and an untreated model control group (model group); while, the non-irradiated mice as the normal control group. SCC or CsA were administered by gastrogavage for 20 days, starting on day 4 after irradiation. Peripheral blood cells were counted and colony-forming fibroblasts (CFU-F) in the bone marrow were assayed. The ability of MSCs to form calcium nodes after culture in osteoinductive medium was also observed. The immunosuppressive effect of MSCs on T lymphocytes was analyzed by enzyme-linked immunosorbent assay and flow cytometry, to evaluate the efficacy of SCC in mice with aplastic anemia. Results: Peripheral blood white cell and platelet counts were increased by medium and high SCC doses, compared with the untreated control. CFU-Fs were also increased compared with the untreated control, and the numbers of calcium nodes in MSCs in osteoinductive medium were elevated in response to SCC treatment. The percentage of Forkhead box protein 3 (FOXP3+) T cells was increased in T cell-MSC cocultures, and the cytokine transforming growth factor β1 was up-regulated in SCC-treated groups. Conclusion : The results of this study suggest that SCC not only promotes the proliferation and differentiation of MSCs, but also improves their immunoregulatory capacity in mice with aplastic anemia.  相似文献   

10.
Background Mycophenolate mofetil (MMF) and cyclophosphamide (CTX) are widely used in treating various kidney diseases.However,whether they are effective and which one is better for treating IgA nephropathy patients with proliferative pathological phenotype in renal diseases,such as endocapillary proliferation,cellular crescents,and/or capillary loops fibrinoid necrosis is still unknown.We,therefore,initiated a study to compare the effects of MMF and CTX in treating IgA nephropathy with the above pathological lesions.Methods One hundred and nineteen patients with IgA nephropathy who had at least one of the three aforementioned lesions were enrolled.All patients were treated with prednisone; 48 patients received prednisone only (Pred group),40 received MMF and prednisone (MMF + Pred group),and 31 were treated with CTX and prednisone (CTX + Pred group).The median time of follow-up was 30 months (maximum:96 months).The primary endpoint was defined as renal survival.The incidence of remission of proteinuria was the secondary endpoint.Results Serum creatinine in all groups declined significantly at different follow-up times (P=0.002),and the differences among the three groups were significant (P<0.001).At 24 months of follow-up,the decline rates were 12.35%,32.95%,and 24.14% in the Pred,MMF + Pred,and CTX + Pred groups respectively.For urine protein excretion,the decline rates were 49.12% (Pred),73.67% (MMF + Pred),and 63.53% (CTX + Pred) respectively at 24 months of follow-up.The differences among the three groups were not significant (P=0.714).Renal survival (the primary endpoint) was significantly different (P=0.027); however,the sencondary endpoint was similar for all the three groups (P=0.100).Conclusions For IgA nephropathy patients with endocapillary proliferation,cellular crescents,and/or fibrinoid necrosis of capillary loops,prednisone combined with MMF was more effective in lowering the serum creatinine than with CTX.Combined MMF and orednisone treatment led to a better renal survival compared to that of prednisone with CTX.  相似文献   

11.
目的:探讨抗T细胞受体(T cell receptor, TCR)αβ单抗和抗CD80单抗联合供体骨髓细胞输注方法在同种异基因小鼠皮肤移植耐受诱导中的作用.方法:第0天,向C57BL/6小鼠(受体)尾静脉输注2×108个BALB/c小鼠(供体)来源的骨髓细胞,同时腹腔注射抗TCRαβ单抗500 μg;第2天,向C57BL/6小鼠腹腔注射抗CD80单抗500 μg.第6天进行皮肤移植.在不同的时间对C57BL/6小鼠进行迟发型超敏反应测定和混合淋巴细胞反应(mixed lymphocyte reaction, MLR)分析,并进行MLR的白细胞介素-2(interleukin-2, IL-2)逆转实验、过继转移实验和嵌合体检查,探讨耐受形成的机制.结果:接受了抗TCRαβ单抗和抗CD80单抗联合供体骨髓移植的C57BL/6小鼠,供体皮肤移植物平均存活70 d;在迟发型超敏反应和混合淋巴细胞反应中均表现出显著的低反应性.IL-2逆转实验结果表明克隆不应答可能参与了移植耐受的形成.体内、体外过继转移实验均显示耐受C57BL/6小鼠脾细胞中存在抑制细胞的活性.嵌合体检查结果表明在耐受C57BL/6小鼠的胸腺和脾中均形成了混合嵌合体,嵌合体水平随时间下降.结论:抗TCRαβ单抗和抗CD80单抗联合大剂量供体骨髓细胞输注可以在组织相容性抗原完全不相同的成年小鼠间成功诱导出皮肤移植物的长期耐受.  相似文献   

12.
黄芪在同种移植排斥中对CD4+ CD25+ T细胞及Foxp3的影响   总被引:4,自引:0,他引:4  
探讨黄芪(AST)在同种移植排斥中对CD4+CD25+T细胞动态变化及Foxp3表达的影响。方法:C57BL/6和BALB/c小鼠分别为供体和受体,建立皮肤移植模型。对照组:术后注射生理盐水;AST组:术后给予黄芪注射液;AST+脾细胞(SP)组:术前输注供体鼠脾细胞,术后给予黄芪注射液,CsA+SP组:术前输注供体鼠脾细胞,术后给予环孢素A(CsA)。术后逐日观察移植皮肤存活情况及小鼠一般状况;免疫荧光染色流式细胞术检测脾组织中CD4+CD25+T细胞动态变化;RT PCR检测Foxp3mRNA表达情况。结果:与对照组相比,AST组、AST+SP组、CsA+SP组移植皮片存活时间明显延长(P<0.05),移植后14?d,CD4+CD25+T细胞数量及Foxp3的相对表达量显著增多(P<0.05)。结论:黄芪体内用药可延长同种移植物的存活时间,上调CD4+CD25+T细胞及Foxp3的活性。  相似文献   

13.
目的:探讨用基因工程方法表达的人可诱导共刺激分子(ICOS)与小鼠免疫球蛋白的融合蛋白竞争抑制ICOSB7RP1共剌激通路的作用.方法:以RT-PCR方法克隆编码人ICOS胞外片段,与编码小鼠免疫球蛋白IgG恒定片段(Ig)的基因融合,构建携带融合基因的高效真核表达载体pcDNA4/HisMAX A-ICOS-Ig.采用脂质体法转染CHO细胞,用Western 印迹法检测稳定表达细胞中融合基因的表达,流式细胞术检测重组蛋白的配体结合活性.以适当浓度的重组融合蛋白作为拮抗剂与BALB/c和C57BL小鼠脾单个核细胞进行混合培养,观察重组蛋白在体外抑制淋巴细胞增殖的效果.结果:构建了携带融合基因的高效真核表达载体pcDNA4/HisMAX A-ICOS-Ig;Western印迹法检测表明转染细胞有重组蛋白的表达;流式细胞术分析显示重组蛋白有配体表达细胞的结合活性;该重组融合蛋白作为拮抗剂可体外抑制混合淋巴细胞增殖.结论:构建并成功表达了ICOS-Ig融合基因高效真核表达载体;该重组蛋白具有配体结合活性,可在体外通过抑制ICOS-B7RP1共刺激通路抑制淋巴细胞增殖.  相似文献   

14.
In the p~ess of allograft rejechon, the interactionbetween multiple adhesitin molecules Promotes the development Of the inflallnnatory ~on that leads to aliceddestruchon. Ih both aamal and hUInan models of aliced~splantation, the expression of adheSion molecules, including letlkocyte funchon-associated antigen-l (on-l ),intel'Cellular adhesion molecule-l (ICal-l ), vascularcell adhesion molecule~l (VCAM~l) and CD44 over thesurfaCe of the endothelial cells has been shown tO increasedwi al…  相似文献   

15.
用伴刀豆蛋白A(Con A)体外诱导的T淋巴母细胞免疫同系小鼠获得的抗体,能与不同品系小鼠的T淋巴母细胞和杀伤性T淋巴细胞株(CTLL2)起结合反应,并能抑制CTLL2细胞的增殖,阻断Con A诱导小鼠脾细胞转化及混合淋巴细胞反应等生物学特性,结果提示:该抗体具有抗小鼠白细胞介素2受体的特征。  相似文献   

16.
抗独特型抗体对小鼠移植低免疫反应状态的诱导作用   总被引:1,自引:0,他引:1  
目的:探讨抗独特型抗体对小鼠移植耐受的诱导作用。方法:以C57BL/6小鼠脾细胞免疫BALB/c小鼠制备抗同种异品系抗体(Abl),Abl交联KLH后,免疫BALB/c小鼠诱导产生抗独特型多克隆抗体(Ab2),以此为移植受体,观察Ab2对小鼠心脏移植耐受的诱导作用。结果:Abl交联KLH和弗氏佐剂免疫可有效地诱导Ab2,与对照组相比,Ab2诱导组的小鼠移植物存活时间明显延长。结论:移植前在受体体内诱导产生以移植物抗原为模拟抗原的Ab2,可以对小鼠特异性低免疫反应状态起到有效的诱导作用。  相似文献   

17.
利用CFSE标记检测CD8~+淋巴细胞增殖   总被引:3,自引:0,他引:3       下载免费PDF全文
[目的 ]介绍一种新的检测淋巴细胞增殖的方法。 [方法 ]用本室构建的重组蛋白疫苗hsp6 5-CAP3对C5 7小鼠进行 3次免疫后 ,分离小鼠的脾细胞 ,以照射灭活的CAP3转基因细胞为刺激细胞 ,在体外刺激淋巴细胞的增殖反应。淋巴细胞在与刺激细胞共培养之前用绿色荧光染料羧乙基锗倍半氧化物 (CFSE)进行标记。在共培养 72h后 ,用PE标记的抗鼠CD8分子的单抗标记淋巴细胞。收集细胞进行FACS检测 ,出现在二维点图左上象限的细胞代表CFSE含量减少的CD8 淋巴细胞 (CD8 CFSElow)即增殖的CD8 淋巴细胞 ,利用流式细胞仪记数左上象限CD8 CFSElow细胞的比例。 [结果 ]经体外刺激的脾淋巴细胞中 ,实验组CD8 CFSElow的平均百分比值为 (16 .4 7± 2 .10 ) % ,对照组CD8 CFSElow 的平均百分比值为 (7.6 9± 1.6 5 ) % (P <0 .0 5 )。 [结论 ]通过FACS结果判定CD8 淋巴细胞发生了特异性的增殖。CFSE标记是一种有效的检测淋巴细胞增殖的方法。  相似文献   

18.
目的观察比较Tju103和CTLA4-Ig分别调节、诱导T淋巴细胞免疫耐受的作用.方法用经丝裂霉素处理的异基因正常BALB/c(H-2d)小鼠巨噬细胞做耐受诱导原,分别用Tju103和CTLA4-Ig体外训导、调节C57BL/6(H-2d)小鼠T淋巴细胞,通过增殖效应(单向混合淋巴细胞反应,MLR)和杀伤效应(MTT法),考察经训导的C57BL/6小鼠T淋巴细胞分别对BALB/c小鼠和CBA(H-2k)小鼠脾细胞以及EL9611(H-2d)红白血病细胞的增殖效应和杀伤效应的改变.结果经Yju103调节后,C57BL/6 小鼠T淋巴细胞对BALB/c和CBA小鼠脾细胞以及EL9611红白病细胞的增殖反应和杀伤效应抑制作用明显,未能诱导对已接触抗原(BALB/c小鼠)产生特异性免疫耐受.经CTLA4-Ig孵育后,C57BL/6 小鼠T淋巴细胞对这三种细胞的增殖反应和杀伤效应抑制作用明显;对已接触抗原呈现免疫耐受,而对第三种抗原(CBA小鼠)和EL9611白血病细胞保持反应性.结论在特异抗原存在下,Tju103和CTLA4-Ig均能明显抑制异基因小鼠T淋巴细胞增殖反应性和杀伤效应,但Tju103诱导非特异免疫抑制,而CTLA4-Ig诱导特异免疫耐受,更适合于诱导移植免耐受.  相似文献   

19.
小鼠对大鼠异种皮肤移植耐受的诱导   总被引:1,自引:0,他引:1  
目的探索更为温和的适合临床应用的诱导异种移植耐受的方案。方法给小剂量照射( 300 rad)的 C57BL/6 (B6)小鼠静脉注射抗小鼠 CD4单抗 0.5 ml后输注 Lewis大鼠骨髓细胞 ,并联合应用腹腔注射环磷酰胺诱导耐受。于耐受诱导后 30 d对受体小鼠作耐受状态的检查,包括供体特异性皮肤移植、混合淋巴细胞反应( MLR)及迟发型超敏反应( DTH)。并通过过继转移实验、外源 IL- 2对耐受小鼠供体特异性 MLR的影响等进一步探讨耐受形成的机制。结果 Lewis大鼠的皮肤移植物在耐受 B6小鼠中存活期特异性延长, MLR及 DTH检查证明 B6小鼠对 Lewis大鼠的脾细胞产生特异性耐受,对无关第三者 DA大鼠及 BALB/c小鼠的脾细胞仍表现出强烈的免疫应答。体内外过继转移实验表明 ,耐受不能被转移 ,未发现抑制细胞的存在。耐受小鼠供体特异的 MLR可以被外源 IL- 2逆转 ,说明耐受主要不是克隆排除,而与克隆不应答有关。结论应用低剂量照射、骨髓移植、环磷酰胺及抗 CD4单抗等方法法可以有效诱导出小鼠对大鼠的移植耐受。  相似文献   

20.
Background Rapamycin (RAPA) is a relatively new immunosuppressant drug that functions as a serine/threonine kinase inhibitor to prevent rejection in organ transplantation. RAPA blocks activation of T-effector (Teff) cells by inhibiting the response to interleukin-2. Recently, RAPA was also shown to selectively expand the T-regulator (Treg) cell population. To date, no studies have examined the mechanism by which RAPA converts Teff cells to Treg cells. Methods Peripheral CD4+CD25- naive T cells were cultivated with RAPA and B cells as antigen-presenting cells (APCs) in vitro. CD4+CD25- T cells were harvested after 6 days and analyzed for expression of forkhead box protein 3 (Foxp3) using flow cytometry. CD4+CD25+CD127- subsets as the converted Tregs were isolated from the mixed lymphocyte reactions (MLR) with CD127 negative selection, followed by CD4 and CD25 positive selection using microbeads and magnetic separation column (MSC). Moreover, mRNA was extracted from converted Tregs and C57BL/6 naive CD4+CD25+ T cells and Foxp3 levels were examined by quantitative real-time polymerase chain reaction (rt-PCR). A total of 1×105 carboxyfluorescein succinimidyl ester (CFSE)-labeled naive CD4+CD25- T cells/well from C57BL/6 mice were cocultured with DBA/2 or C3H maturation of dendritic cells (mDCs) (0.25×105/well) in 96-well round-bottom plates for 6 days. Then 1×105 or 0.25×105 converted Treg cells were added to every well as regulatory cells. Cells were harvested after 6 days of culture and analyzed for proliferation of CFSE-labeled naive CD4+CD25- T cells using flow cytometry. Data were analyzed using CellQuest software.Results We found that RAPA can convert peripheral CD4+CD25- naive T Cells to CD4+Foxp3+ Treg cells using B cells as APCs, and this subtype of Treg can potently suppress Teff proliferation and maintain antigenic specificity. Conclusion Our findings provide evidence that RAPA induces Treg cell conversion from Teff cells and uncovers an additional mechanism for tolerance induction by RAPA.  相似文献   

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