荷瘤小鼠骨髓来源树突状细胞诱导的抗肿瘤作用

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目的:探讨能否从荷瘤小鼠骨髓细胞诱导出功能正常、具有抗肿瘤作用的树突状细胞(DC),与正常小鼠骨髓来源的DC比较有无差异。方法:于体外用mGM-CSF和mIL-4分别从正常小鼠和CT26结肠腺瘤小鼠的骨髓细胞诱导DC,并用CT26肿瘤细胞抗原冲击致敏。用相差显微镜观察DC的形态学变化;流式细胞术检测CT26肿瘤细胞抗原致敏前后DC表面分子变化;3H-TdR掺入法检测肿瘤抗原致敏DC刺激T细胞增殖的能力;乳酸脱氢酶(LDH)4 h释放法检测肿瘤抗原致敏DC诱导同基因T细胞增殖、分化为细胞毒性T细胞(CTL)的杀伤活性。结果:荷瘤小鼠骨髓来源DC与正常小鼠骨髓来源DC的Ia-Kd、H-2Kd、CD80、CD86I、CAM-1表达水平和它们刺激T细胞增殖的能力以及所诱导产生的CTL杀伤活性均无显著性差异。结论:荷瘤小鼠骨髓来源的DC与正常小鼠骨髓来源的DC具有相似的功能和抗肿瘤作用,提示可以从荷瘤机体的DC前体诱导出具有抗肿瘤作用的DC用于肿瘤的免疫治疗。 Objective: To investigate whether DCs with normal function and antitumor activity can be induced from tumor-bearing mouse bone marrow cells, and whether there is any difference between normal mice and bone marrow-derived DCs. Methods: DCs were induced in vitro from bone marrow cells of normal mice and CT26 colon adenoma mice with mGM-CSF and mIL-4, respectively, and sensitized with CT26 tumor cell antigen challenge. The morphological changes of DCs were observed by phase-contrast microscopy. The changes of DC surface molecules before and after sensitization of CT26 tumor cells were detected by flow cytometry. The ability of DCs stimulated by tumor antigen to stimulate the proliferation of T cells was assayed by 3H-TdR incorporation assay. Lactate dehydrogenase (LDH) 4 h release assay to detect tumor antigen-primed DC induced syngeneic T cell proliferation, differentiation into cytotoxic T lymphocytes (CTL) killing activity. Results: The expression levels of Ia-Kd, H-2Kd, CD80, CD86I and CAM-1 in bone marrow-derived DCs and normal mouse bone marrow-derived DCs in tumor-bearing mice and their ability to stimulate T cell proliferation as well as the induced CTL killing activity No significant difference. CONCLUSION: Bone marrow-derived DCs in tumor-bearing mice have similar functions and anti-tumor effects to DCs derived from normal mice, suggesting that DC with anti-tumor effect can be induced from DC precursors of tumor-bearing mice for tumor immunity treatment.
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