中国病理生理杂志
中國病理生理雜誌
중국병리생리잡지
CHINESE JOURNAL OF PATHOPHYSIOLOGY
2008年
4期
645-649
,共5页
树突细胞%抗原,肿瘤%疫苗%免疫疗法
樹突細胞%抗原,腫瘤%疫苗%免疫療法
수돌세포%항원,종류%역묘%면역요법
Dendritic ceils%Antigens,neoplasm%Vaccines%Immunotherapy
目的:探索肿瘤裂解物负载的DCs诱导活化的初始T细胞介导细胞免疫及活化的T细胞杀死肿瘤细胞的能力.方法:应用黏附法分离外周血中的淋巴细胞和单核细胞,应用GM-CSF+IL-4刺激单核细胞并诱导为iDCs,然后进行分组,应用相应的细胞因子等刺激iDCs转化为mDCs,其中肿瘤裂解物冲击DCs组:冻融抗原负载+TNF-α+IL-1β;无肿瘤裂解物冲击组:TNF-α+IL-1β.再分别用上述DCs与淋巴细胞进行混合培养以刺激混合淋巴细胞中的T细胞转化为细胞毒性T细胞,并进行分组,肿瘤裂解物冲击DCs组:肿瘤裂解物冲击DCs+IL-2+IL-7;无肿瘤裂解物冲击DCs组:无肿瘤裂解物冲击DCs+IL-2+IL-7;对照组:IL-2+IL-7.结果:成功获得iDCs,并高表达CD86、CD80 和 HLA-DR;相对于其它组,肿瘤裂解物冲击DCs组mDCs更显著上调CD83,且更有效地刺激淋巴细胞增殖;肿瘤裂解物冲击DCs组的CTLs也高表达CD95(Fas)且TNF-α和IFN-γ的表达水平显著提高(P<0.05).结论:肿瘤裂解物冲击DCs可有效促进T细胞活化、增殖;并显著增强相应CTLs的杀死靶细胞的能力,这为发展DCs+CTLs的免疫治疗肿瘤提供了一种新而且简便的生物治疗模式.
目的:探索腫瘤裂解物負載的DCs誘導活化的初始T細胞介導細胞免疫及活化的T細胞殺死腫瘤細胞的能力.方法:應用黏附法分離外週血中的淋巴細胞和單覈細胞,應用GM-CSF+IL-4刺激單覈細胞併誘導為iDCs,然後進行分組,應用相應的細胞因子等刺激iDCs轉化為mDCs,其中腫瘤裂解物遲擊DCs組:凍融抗原負載+TNF-α+IL-1β;無腫瘤裂解物遲擊組:TNF-α+IL-1β.再分彆用上述DCs與淋巴細胞進行混閤培養以刺激混閤淋巴細胞中的T細胞轉化為細胞毒性T細胞,併進行分組,腫瘤裂解物遲擊DCs組:腫瘤裂解物遲擊DCs+IL-2+IL-7;無腫瘤裂解物遲擊DCs組:無腫瘤裂解物遲擊DCs+IL-2+IL-7;對照組:IL-2+IL-7.結果:成功穫得iDCs,併高錶達CD86、CD80 和 HLA-DR;相對于其它組,腫瘤裂解物遲擊DCs組mDCs更顯著上調CD83,且更有效地刺激淋巴細胞增殖;腫瘤裂解物遲擊DCs組的CTLs也高錶達CD95(Fas)且TNF-α和IFN-γ的錶達水平顯著提高(P<0.05).結論:腫瘤裂解物遲擊DCs可有效促進T細胞活化、增殖;併顯著增彊相應CTLs的殺死靶細胞的能力,這為髮展DCs+CTLs的免疫治療腫瘤提供瞭一種新而且簡便的生物治療模式.
목적:탐색종류렬해물부재적DCs유도활화적초시T세포개도세포면역급활화적T세포살사종류세포적능력.방법:응용점부법분리외주혈중적림파세포화단핵세포,응용GM-CSF+IL-4자격단핵세포병유도위iDCs,연후진행분조,응용상응적세포인자등자격iDCs전화위mDCs,기중종류렬해물충격DCs조:동융항원부재+TNF-α+IL-1β;무종류렬해물충격조:TNF-α+IL-1β.재분별용상술DCs여림파세포진행혼합배양이자격혼합림파세포중적T세포전화위세포독성T세포,병진행분조,종류렬해물충격DCs조:종류렬해물충격DCs+IL-2+IL-7;무종류렬해물충격DCs조:무종류렬해물충격DCs+IL-2+IL-7;대조조:IL-2+IL-7.결과:성공획득iDCs,병고표체CD86、CD80 화 HLA-DR;상대우기타조,종류렬해물충격DCs조mDCs경현저상조CD83,차경유효지자격림파세포증식;종류렬해물충격DCs조적CTLs야고표체CD95(Fas)차TNF-α화IFN-γ적표체수평현저제고(P<0.05).결론:종류렬해물충격DCs가유효촉진T세포활화、증식;병현저증강상응CTLs적살사파세포적능력,저위발전DCs+CTLs적면역치료종류제공료일충신이차간편적생물치료모식.
AIM:To evaluate the ability of dendritic cells (DCs) loaded with tumor lysate to initiate cell mediated immune responses by stimulating naive T cells, and the efficiency of activated T cells to kill autologous tumor cells in vitro. METHODS: The peripheral blood lymphocytes and monocytes were obtained from the advanced renal cell carcinoma patient by eonglutination method. The immature dendritic cells were generated in the presence of interleukin -4(IL-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF) from monocytes of healthy individuals.These cells were pulsed with tumor lysate or not. Induction of tumor-specific cytotoxic T lymphocytes(CTLs) response by mature dendritic cells (mDCs) was evaluated by the CD95(Fas) expression assay through FCM and the cytotoxic assay a gninst autolognns human tumor cells. RESULTS: Human immature dendritic cells and T cells obtained from healthy donors were stimulated with tumor- pulsed dendritic cells. The immature dendritic cells were applied to the cytotoxicity assay a gainst target autologons tumor cells. The CD95 (Fas) expression, IFN-γ, and TNF -α secreted by the CTLs in tumor lysate-plused DC group were higher than those of other groups. The capacity of the CTLs to kill autolognns tumor cells was significantly different(P<0. 05). Antigen-specific DCs vaccine can induce T cells activation and proliferation, thus we can obtain higher proportion of tumor specific cytotoxic T cells(CTLs), and enhance the CTLs to secret IFN-γ and TNF-α. CONCLUSION: Our results indicate that monocyte-derived human dendritic cells pulsed with tumor lysate could in duce the specific antitumor effect against autologons tumors. This in vitro model offers a new and simple approach to the development of DC + CTL - based immunotherapy.
