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1.
胸腺肽α1治疗重症肝炎的免疫调节研究 总被引:7,自引:1,他引:6
为了解日达仙的免疫调节作用,选取18例下肝炎病人用日达仙(Tα1)治疗,并在治疗前后检测内毒素(LSP)、肝瘤坏死因子(TNF)、白细胞介素2受体(IL-2R)、白细胞介素4(IL-4)、白细胞介素6(IL-6)、及T细胞亚群(CD8^+、CD4^+)。结果治疗前LSP、TNF、IL-2R、IL-6、CD8^+均增高9P〈0.01),而IL-4及CD4^+降低。经Tα1治疗后LSP、TF、IL-2 相似文献
2.
芪黄冲剂对慢性乙型肝炎患者免疫功能的影响 总被引:16,自引:0,他引:16
目的:观察芪黄冲剂对慢性乙型病毒性肝炎免疫功能的影响。方法:治疗组以芪黄冲剂治疗,对照组以乙肝清热解毒冲剂合乙肝养阴活血冲剂治疗。两组患者采用间接免疫荧光法检测,治疗前后免疫球蛋白IgG、IgM、IgA、T淋巴细胞亚群CD3^+、CD4^+、CD8^+、CD4^+/CD8^+、IL-2、IL-6、TNF、NK。结果:芪黄冲剂具有益气活血,滋养肝肾兼以清热解毒作用,能升高CD4^+、NK细胞,提高CD4^+/CD8^+比值及IL-2水平,降低CE8^+,尤其对CD4^+、CD4^+/CD8^+、NK细胞以及IL02的调整作用优于对照组(P〈0.05 ̄0.01),能显著降低IL-6及TNF水平(P〈0.05 ̄0.01)。同时还能降低IgG、IgM、IgS,其中对IgA的降低作用显著优于对照组。结论:芪黄冲剂不仅具有 相似文献
3.
旋毛虫感染小鼠IgG,IL—2和T淋巴细胞亚群动态变化的 … 总被引:1,自引:0,他引:1
目的 了解小鼠感染旋毛虫后IgG抗体水平、IL-2分泌量和T淋巴细胞亚群的动态变化。方法 分别于旋毛虫感染后第7、14、21、28和35天,采用ELISA方法检测血甭特异性IgG抗体水平和IL-2含量,采用流式细胞仪检测CD4^+、CD8^+T细胞百分率。结果 IgG抗体水平在感染后逐渐上升,感染后35天达最高值;T淋巴细胞的变化表现为CD4^+细胞减少、CD8^+T细胞增多,CD4^+/CD8^ 相似文献
4.
肝硬化和肝细胞癌患者血清IL-2、sIL-2R、IL-6、T细胞亚群的变化及相互关系 总被引:6,自引:0,他引:6
目的研究肝硬化和肝细胞癌患者IL-2、sIL-2R、IL-6、T细胞亚群的变化和相互关系。方法分别采用双抗体夹心ELISA法、ABS-ELISA法和红细胞花环实验,对46例肝炎肝硬化和肝癌进行了IL-2、IL-6、sIL-2R和T细胞亚群的测定,并与66例健康献血员进行了对照。结果肝炎肝硬化(LC)、肝细胞癌(HCC)患者血清IL-2、CD+4/CD+8水平明显低于正常对照(NC)组(P<001),而IL-6、sIL-2R水平明显升高,HCC组的平均IL-6水平高出正常10倍以上,较肝硬化组明显升高(P<001)。在肝炎肝硬化和肝癌患者均发现IL-2与CD+4/CD+8比值、IL-6与sIL-2R正相关,IL-6与CD+4/CD+8比值显著负相关,而与IL-2无相关关系。结论肝炎肝硬化和肝细胞癌患者存在免疫功能紊乱和低下、淋巴因子网络失衡,这与其病理生理机制有关,也为临床上LC、HCC应用IL-2治疗提供了理论依据。IL-6的显著增高有助于HCC的早期诊断 相似文献
5.
肝舒胶囊对慢性肝炎患者免疫功能的影响 总被引:1,自引:0,他引:1
为探讨肝舒胶囊对慢性肝炎患者免疫功能的调节作用,检测了肝舒胶囊治疗前后慢性肝炎患者的T淋巴细胞亚群,自然杀伤细胞及血清可溶性白细胞介素-2受体等指标,并以健康献血者为对照。结果肝炎组CD^+3,CD^+4,CD^+3/CD^+4,CD^+57显著下降,CD^+8,sIL-2R显著增高,经过肝舒胶囊治疗后,呈相对应负性改变。提示肝舒胶囊对免疫功能有显著改善和调节作用。 相似文献
6.
目的 探讨肺癌瘤浸润淋巴细胞(TIL)的分离、培养增殖特性,杀伤活性,表型变化及回输病人后的临床毒副反应。方法 应用机械、酶消化法从63例肺癌患者手术切除的实体瘤中分离得到TIL,其中51例经IL-2体外激活培养,12例在培养前后应用^3H-TdR释放实验测定TIL对自体瘤细胞和801-D细胞的杀伤作用,13例用间接免疫荧光法测定淋巴细胞表型CD3^+、CD4^+、CD8^+比例的变化。15例病人 相似文献
7.
本研究对12例拟行APBSCT的患者予VCR1-2mg/m2,体表面静注及CTX7g/^2体表面积静滴,5-7天后予G-CSF100μg/m^2体表面积静注5-7天,白细胞升至3.0×10^9/L以上时,用CS3000血细胞分离机单次收集单个核细胞MNC〉2.8×10^8/kg,CD^+34〉.6×10^6/kg,CFU-GM〉3.9×1-0^4/kg,APBSCT后,全部患者于+5天-+10天白 相似文献
8.
对28例未经任何治疗的中晚期原发性肝癌患者进行免疫功能的检测,并与正常比较,结果发现其IL-2系统中IL-2产生能力显著性降低,T淋巴细胞mIL-2R表达非常显著性降低,而血清sIL-2R水平非常显著性增加;外周血淋巴细胞绝对数及T淋巴细胞亚群分析表明前者明显降低,CD4细胞,CD4/CD8比值非常显著性降低,CD8细胞呈显著升高,相关性分析表明:sIL-2R水平与CD4细胞,CD4/CD8比值呈 相似文献
9.
乙型肝炎患者免疫促进剂治疗前后T淋巴细胞亚群及NK细胞的… 总被引:1,自引:0,他引:1
对62例慢乙肝患者T淋巴细胞亚群及NK细胞检测,并观察分别经iRNA、猪苓多糖及LAK细胞治疗前后的细胞数量变化。结果发现治疗前CD^+4细胞降低,CD^+8细胞增高。CD^+4/CD^+8比值下降。治疗后CD^+4细胞及NK细胞增高,CD^+4/CD^+8比值上升,其中以LAK细胞治疗效果显著,与HBVM转阴呈正相关。说明提高机体免疫功能对清除病毒有一定作用。 相似文献
10.
11.
Joji Kitayama Hirokazu Nagawa Hiroshi Nakayama Nelson Tuno Yoichi Shibata Tetsuichiro Muto 《Journal of gastroenterology》1999,34(3):327-333
Integrins play an important role in various lymphocyte functions. In this study, tumor-infiltrating lymphocytes (TIL) were
isolated from colorectal cancer tissues and the expression of β1 and β2 integrins on the TIL was quantitatively examined with
two-color flow cytometry. In comparison with peripheral blood lymphocytes (PBL), TIL expressed a lower level of common β1
chain (CD29) in both CD4 and CD8 sub-populations. Among the associated α chains, the expressions of α1 (CD49a) and α2 (CD49b)
were slightly higher in TIL than in PBL, whereas α4 (CD49d) and α6 (CD49f) were markedly downregulated in TIL. Both αL (CD11a)
and β2 (CD18) were reduced in CD8(+) TIL but not in CD4(+) TIL. TIL with the CD8(+) cytotoxic phenotype showed significantly
decreased binding to purified intracellular adhesion molecules (ICAM)-1, and vascular adhesion cell molecule (VCAM)-1, and
HT29 colon cancer cells, compared with the in counterparts in PBL. The peculiar expression pattern and functional down regulation
of these integrins may explain why TIL in colorectal cancer cannot eradicate the malignant cells.
Received: August 24, 1998/Accepted: November 27, 1998 相似文献
12.
Chaperot L Manches O Mi JQ Moine A Jacob MC Gressin R Molens JP Sotto JJ Leroux D Bensa JC Plumas J 《British journal of haematology》2002,119(2):425-431
We have previously reported that specific anti-tumour cytotoxic T cells (CTL) can be differentiated from tumour-infiltrating lymphocytes (TIL) in non-Hodgkin's lymphoma. We found that the combination of interleukin (IL)-1, IL-2 and IL-12 was very efficient for expansion of CD8+ T-cell receptor (TCR)alphabeta+ T cells and for development of their ability to specifically lyse tumour cells. In this study, we investigated whether anti-tumour T cells could be generated from the peripheral blood of patients using the culture protocol developed for TIL. Autologous T cells and tumour B cells from five patients were included in this study. It was found that polyclonal anti-tumour cytotoxic effector cells were generated when cultured in the presence of IL-1beta, IL-2 and IL-12. Interestingly, tumour cells were lysed by perforin/granzyme-mediated cytolysis and not by CD95-mediated apoptosis. By performing inhibition experiments, it was observed that both CD8+ and CD4+ T cells were responsible for the cytotoxic effect and that they were able to recognize malignant B cells by either a major histocompatibility complex (MHC)-restricted or MHC-non-restricted mechanism. Intriguingly, in addition to interferon-gamma and tumour necrosis factor-alpha, IL-10 was secreted continuously during culture. The source of patient T cells used for the generation of anti-tumour CTL should be based on the results obtained with peripheral blood lymphocytes and TIL. 相似文献
13.
14.
AIM: To investigate the role of tumor infiltrating lymphocytes (TIL) in primary hepatocellular and cholangiolar carcinomas of the liver.METHODS: Immunohistochemical analysis was performed including antibodies to CD3, CD4, CD8, CD20, CD56 and TIA-1 in formalin-fixed and paraffin-embedded tissue of 35 liver resection specimens of hepatocellular or cholangiocellular carcinomas. Semiquantitative evaluation was performed with emphasis on the area of the tumor itself and of the tumor/liver interface.RESULTS: All hepatocellular carcinomas showed infiltration of lymphocytes predominantly around the tumor in the tumor/liver interface consisting mainly of CD3+ CD4+ T lymphocytes [164.3/10 high power fields (HPF)] and in the tumor itself of CD8+ cells (54.9/10 HPF). Cholangiocarcinomas contained a heterogeneous amount of TIL, composed mainly of CD3+ T cells with a predominance of CD8+ cells in the tumor tissue (52.6/10 HPF) and of CD4+ cells in the interface region (223.1/10 HPF). CD56+ cells of the innate immune system were scarce. There was no significant difference between hepatocellular or cholangiolar carcinoma. No correlation with the clinicopathological data was seen. CONCLUSION: Liver TIL consists of intratumoral CD8+ T cells and peritumoral CD4+ T cells independent of histogenetic origin. Different functions of lymphocytes in these regions seem possible. 相似文献
15.
Hans-Udo Kasper Uta Drebber Dirk Ludger Stippel Hans Peter Dienes Anton Gillessen 《World journal of gastroenterology : WJG》2009,15(40):5053-5057
AIM: To investigate the role of tumor infiltrating lymphocytes (TIL) in primary hepatocellular and cholangiolar carcinomas of the liver.METHODS: Immunohistochemical analysis was performed including antibodies to CD3, CD4, CD8, CD20, CD56 and TIA-1 in formalin-fixed and paraffin-embedded tissue of 35 liver resection specimens of hepatocellular or cholangiocellular carcinomas. Semiquantitative evaluation was performed with emphasis on the area of the tumor itself and of the tumor/liver interface.RESULTS: All hepatocellular carcinomas showed infiltration of lymphocytes predominantly around the tumor in the tumor/liver interface consisting mainly of CD3+ CD4+ T lymphocytes [164.3/10 high power fields (HPF)] and in the tumor itself of CD8+ cells (54.9/10 HPF). Cholangiocarcinomas contained a heterogeneous amount of TIL, composed mainly of CD3+ T cells with a predominance of CD8+ cells in the tumor tissue (52.6/10 HPF) and of CD4+ cells in the interface region (223.1/10 HPF). CD56+ cells of the innate immune system were scarce. There was no significant difference between hepatocellular or cholangiolar carcinoma. No correlation with the clinicopathological data was seen. CONCLUSION: Liver TIL consists of intratumoral CD8+ T cells and peritumoral CD4+ T cells independent of histogenetic origin. Different functions of lymphocytes in these regions seem possible. 相似文献
16.
The phenotypic characteristics of freshly isolated tumor-infiltrating lymphocytes (TIL) obtained from human liver tumors were analyzed by two-color flow cytometry. TIL consisted of mainly CD3+ T-lymphocytes (70-80%). The ratio of CD4/CD8 in TIL from primary and metastatic liver tumors and autologous peripheral blood lymphocytes (A-PBL) was 1.3, 1.1 and 1.3, respectively. The majority of CD3+ T-lymphocytes (mean +/- SD; 95 +/- 11%) expressed T-cell antigen receptor (TCR) alpha/beta, and gamma/delta TCR positive T-cells were only 5 +/- 4.5% in TIL from both primary and metastatic liver tumors. TIL showed significantly higher percentages of transient activation markers, such as CD25 (Tac) and HLA-DR, than A-PBL. TIL also contained significantly more populations of CD3+ CD45RO+ T-lymphocytes, which are considered to be expressed on primed (memory) T-lymphocytes, than A-PBL. Furthermore, TIL from primary liver tumors demonstrated significantly higher percentages of CD3+ CD45RO+ T-cells than those from metastatic liver tumors. These data indicate that TIL from human liver tumors are an apparently distinct population from A-PBL, and that local immune responses against human primary and metastatic liver tumors might be different. Moreover, TIL from primary liver tumors consisted of mainly activated or primed (memory) T-cells, suggesting that they were sensitized and activated by autologous tumor cells in vivo. These observations may imply the possibility of adoptive immunotherapy using TIL against human primary liver tumors. 相似文献
17.
A study was conducted to investigate the time course of changes in phenotypes of cultured tumor-infiltrating lymphocytes (TIL) isolated from 5 patients with colorectal cancer. Following initial incubation with protein phytohemagglutinin (PHA-P, final concentration 0.1 w/v%), one of the inducers of interleukin-2 (IL-2) receptor, and recombinant interleukin-2 (rIL-2, 1000U/ml) for 3 days, TIL was further cultured with rIL-2 alone for another 46 to 79 days. Phenotypes of cultured TIL were analyzed by a two color flow-cytometry. The following results were obtained: 1) Yields of TIL isolated from cancerous tissues were 1.0 x 10(6) to 1.6 x 10(6) cells/g wet weight, and TIL grew 31 to 3700 folds in the entire period of culture. These growth rates were significantly higher than those obtained by the conventional method of culture with rIL-2 alone (1 to 720 folds). 2) The population of cytotoxic T cells (CD8(+), CD11(-)) reached the maximum (92%, median value) at 5 weeks of culture, and thereafter gradually decreased to 61% at 9 and 10 weeks. In contrast, the population of activated natural killer cells (CD16(+) and Leu7 (+) or (-)) remained below 4% for the entire period of culture. 3) Maximum enhancement of specific cytotoxic activities of cultured TIL was observed during 3 to 4 weeks in culture, using K562 cells as well as Daudi cells as target cells. In conclusion, addition of PHA-P seems to beneficially affect the growth rate of TIL in culture.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
18.
Li Chun Xu Zhi Lin Chen Zhen Hua Sun Xiang Yu Xu Ming Sheng Wu Shu Biao Ding 《World journal of gastroenterology : WJG》2000,6(3)
AIM To study the effect of immune treatment on gastric cancer.METHODS Thirteen patients with advanced gastric cancer were given TIL adoptive immunotherapy in thisstudy. Histological findings showed that 13 patients had gastric adenocarcinoma. Patients received operationson their primary tumor, which could not be resected. Small tumor tissue and metastic lymph nodes were gotduring the operation for TIL preparation. Ten patients were treated as control group. During TILtreatment, the patients did not received any other treatment. Surgical speciments (metastatic lymph nodes )with pathological diagnosis were obtained from operating room. The lymph nodes were minced anddissociated in RPMI 1640 with 0.03% hyaluronidase type V (1500U/g), 0.05% collagenase type Ⅳ(200 U/g), and 0.008% deoxyribonuclease type I (100 U/g) (Sigma, USA) at 37℃ for 12 h. The cellmixture was then filtered through 4-layer gauge, washed twice in Hank's and separated on Ficoll-Hypague(Shanghai ist Chemical Reagent Factory) at 900×g for 20min. Finally, the cells were harvested andcounted. Cells suspension containing TIL and tumor cells were extensively washed and resuspended at a finalconcentration of 106 lymphocytes/mL in complete medium containing 15% human AB serum, 100 U/mLpenicillin and 100 μg/mL streptomycin in RPMI 1640 (Gibco). The final concentration of rIL-2 (Military Medical Institute, Nanjing ) was 500 U/mL. Cultured after 3 d-4 d, lymphoid cells were counted andculture was separated into more flasks when the concentration of lymmphoid cells reached or exceeded 2×106/mL until the total amount reached about 5×109/mL cells. Cytotoxic activities of TIL were tested by 6 h51Cr-release assay. Target cells (5×10s/mL) (human gastric adenocarcinoma) in 1 mL of culture mediumwere labelled with 100 μci of Na251CrO4(Beijing Atomic Energy Research Institute, Beijing), washed andadjusted to 105cells/mL. Labelled cells (E/T: 50: 1, 25: 1 and 12.5: 1) were seeded in round-bottom microtest plates (Corning, Japan) at 104cells/well. Isotope release was measured in a gamma counter (Packard,USA). The percentage of cytotoxicity was calculated according to the following formula: Cytotoxicity% = (Experimental- Spontaneous)/ (Maximum-Spontaneous)×100. Target cells without effective cells weremixed with 0.1 mL of culture media to obtain spontaneous release, and with 0.1 mL of 0.1 mol/L HCl toobtain maximum 51Cr release. TIL cells so induced were counted, washed twice, resupended in 100 mL 0.9%NaC1 solution and intravenouslly transferred. The number of total autologous TIL cells injected was morethan 5×109 cells for one patient and usually separated into 2 - 3 injection during the treatment, rIL-25000 U/d (Nanjing Military Medical institute, Nanjing) in 2 mL of 0.9% NaCl solution was intramuscularlyinjected starting from 5 days before TIL cells transfer to 5 days after transfer of TIL cells. All patients weregiven scheduled gastric roentgenograms. CT scanning, B type ultrasound, histological examination andimmune function were used to observe the changes before, during and after treatment. The curative effectswere judged by the standard of WHO. The methods of the assays of SIL-2R, NK cytotoxicity and CD4/CD8were carried out respectively according to the references.RESULTS The Nk cytotoxicity and CD4/CD8 were significantly increased (P<0.01) after 3- 6 monthstreatment. The soluble IL-2 receptor in sera of patients was significantly decreased (P<0.01) after 3- 6months treatment. There were no significantly differences in the test of CD4/CD8, the cytotoxicity of Nkcells and the soluble IL-2 receptor in serum between the group before treated by TIL and the control group(P >0.05). The NK cytotoxicity and CD4/CD8 in patients treated by TIL were significantly more than thosein the control group. On the contrary, the soluble IL-2 receptor in serum of patients treated by TIL wassignificantly less than those in serum of the control group. The patients of control group survived from 4.5months to 9 months (less than one year) after operation. However seven of the thirteen patients treated byTIL after operation survived over one year. Appetite was improved, sinew enhanced, weight increased andpain relieved in most of patients treated by TIL. On the contrary, the symptoms and signs of patients ofcontrol group were not improved. According to the standard of WHO, there were significantly differences ofPD(Disease Progress), MR (Minor remission), and PR(partial remission) between TIL group and controlgroup. The results indicated that tumor focus completely disapeared in 1(80%) of 13 patients, significantlydecreased in 4 (30%) of 13 patients and slightly decreased in 7 (53%) of 13 patients, suggesting that thetreatment of TIL in the patients with advanced cancer was effective. No side effects were found except fortransient fever in 2 patients.CONCLUSION TIL should be one of the fundamental therapies for the advanced gastric cancer, it canregulate the balance of immunity, relieve pain, improve symptoms and signs and prolong survival time. 相似文献
19.
Steger Günther G. Gnant Michael F. Djavanmard Manuela P. Mader Robert M. Jakesz Raimund Pierce William deKernion Jean B. Figlin Robert Belldegrun Arie 《Journal of cancer research and clinical oncology》1997,123(6):317-324
Clinical trials utilising interleukin (IL)-2 with tumor-infiltrating lymphocytes (TIL) have demonstrated efficacy in the treatment of metastatic renal cell carcinoma (RCC). Several cytokines, as well as growth factors have demonstrated modulatory effects upon the biological properties of TIL from RCC, suggesting a potentially important role for cytokines other than IL-2 in the development of active and tumor-specific TIL. IL-12 was recently characterized as a natural-killer-cellstimulatory factor or cytotoxic-T-cell-maturation factor. These properties of IL-12 prompted us to investigate the impact of this cytokine upon the activation of TIL from human RCC. In an attempt to enhance the in vitro growth and activity of renal TIL, we have grown eight renal TIL cultures in varying concentrations of IL-2 (8, 40, 80, 400 U/ml) and IL-12 (200 U/ml). In addition, IL-12 (200 U/ml) was added to TIL cultures pre-activated with IL-2 (400 U/ml). Growth, cell expansion, and the ability of TIL to release certain cytokines upon tumor stimulation were determined. Proliferation assays, phenotypic analysis, and cytotoxicity assays were performed at an early and a late culture stage. IL-12, alone and when added to suboptimal concentrations of IL-2, failed to induce TIL growth. While the addition of IL-12 to optimal doses of IL-2 suppressed TIL culture expansion, sequential culture exposure first to IL-2 and then to IL-2+IL-12 increased the number of cells expressing CD3+/CD56+ and these cultures demonstrated enhanced in vitro lysis of autologous tumor. IL-12 clearly demonstrated a sequence-dependent impact of the biological behaviour of TIL from RCC. The optimal use of IL-12 in the in vitro expansion of renal TIL may result in cells with an enhanced specific anti-tumor effect.Abbreviations
IL
interleukin
-
TIL
tumor-infiltrating lymphocytes
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RCC
renal cell carcinoma
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NK
natural killer
-
IFN
interferon
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TNF
tumor necrosis factor
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GM-CSF
granulocyte/macrophage-colony-stimulating factor
-
LAK
lymphokine-activated killer cells 相似文献
20.
Human colorectal tumour infiltrating lymphocytes express activation markers and the CD45RO molecule, showing a primed population of lymphocytes in the tumour area. 总被引:3,自引:2,他引:3
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This study investigated the phenotype of freshly isolated human tumour infiltrating lymphocytes (TIL) from 14 patients with colorectal tumours, and compared them with lymphocytes derived from the lamina propria of the unaffected mucosa and with lymphocytes derived from peripheral blood of the same patients. It was found that TIL expressed the activation markers CD25 and HLA-DR to a higher extent than the peripheral blood lymphocytes (p = 0.01), and that both lamina propria lymphocytes and TIL preferentially expressed the CD45RO + phenotype, associated with memory cells, in contrast with peripheral blood lymphocytes [corrected]. Both lamina propria lymphocytes and TIL contained few natural killer (NK) cells (CD3-CD56+) compared with peripheral blood lymphocytes (p = 0.001), and this was reflected in the cytotoxicity assays. After 1 to 2 weeks in culture with interleukin-2 100 U/ml, lymphocytes from all three compartments had a high cytolytic activity against all targets tested, consistent with the lymphokine activated killer cell phenomenon. No increase in the number of NK cells was noted after culture, but 20-30% of the T cells now coexpressed the CD56 molecule. This was most prominent in the CD8+ subset, but lymphokine activated killer cell activity was found in both CD4+ and CD8+ subsets. Possible tumour escape mechanisms are discussed. 相似文献