儿童急性淋巴细胞白血病治疗前后外周血T细胞表面CTLA-4、CD28的表达
发布时间：2019-04-27 07:44
【摘要】：目的：探讨外周血T淋巴细胞表面CTLA-4/CD28的表达与儿童急性淋巴细胞白血病(ALL)发病及治疗转归的相关性。 方法：采用流式细胞仪(FCM)技术分别检测27例B细胞型ALL患儿初发且未治疗前、经VDLD方案治疗达到完全缓解并持续缓解予CAT巩固停药2-3周后外周血T淋巴细胞表面CTLA-、CD28的表达。 结果：①治疗前：ALL患儿外周血CD4+、CD8+T淋巴细胞CTLA-4表达显著高于正常(P0.01)；②治疗前：ALL患儿外周血CD4+、CD8+T淋巴细胞CD28表达显著低于正常(P0.01)；③治疗后：诱导敏感ALL患儿在达到完全缓解时外周血CD4+、CD8+T淋巴细胞CTLA-4的表达显著低于治疗前(P0.01),与正常对照组比较均没有统计学意义(P0.05)；④治疗后：诱导敏感ALL患儿在达到完全缓解时外周血CD4+、CD8+T淋巴细胞CD28的表达显著高于治疗前(P0.01),与正常对照组比较均没有统计学意义(P0.05)；⑤治疗后：诱导不敏感ALL患儿在达到完全缓解时外周血CD4+、CD8+T淋巴细胞CTLA-4、CD28的表达与治疗前比较均无显著变化(P0.05)。 结论：①儿童B细胞型ALL初发时T细胞活化的刺激信号CD28表达下降,活化抑制信号CTLA-4表达升高,提示T淋巴细胞不能被充分活化,对肿瘤的免疫监视与清除功能降低,可能是ALL的发病因素之一；②强的松诱导敏感ALL患儿在达到完全缓解时CTLA-4/CD28的表达恢复正常,诱导不敏感ALL患儿在达到完全缓解时CTLA-4/CD28仍然异常表达,推测T淋巴细胞的活化受抑与儿童ALL发病互为因果,可能白血病细胞在发生发展过程中产生免疫封闭因子,使T淋巴细胞不能正常活化,肿瘤细胞易于逃逸；③ALL化疗过程中注重调节T淋巴细胞的免疫功能、刺激T淋巴细胞正常活化可能有助于提高ALL的治疗缓解率,另外持续的CTLA-4/CD28的异常表达可能是ALL不良预后的指标之一
[Abstract]:Aim: to investigate the relationship between the expression of CTLA-4/CD28 on peripheral blood T lymphocyte surface and the pathogenesis and treatment outcome of childhood acute lymphoblastic leukemia (ALL). Methods: flow cytometry (FCM) technique was used to detect the surface CTLA-, of peripheral blood T lymphocytes in 27 children with B cell type ALL before and after treatment with VDLD regimen. The complete remission was achieved by VDLD regimen and sustained remission was achieved after CAT consolidation and withdrawal of drugs for 3 weeks. Expression of CD28. Results: (1) before treatment, the expression of CD4 and CD8 T lymphocyte CTLA-4 in peripheral blood of ALL children was significantly higher than that of normal children (P0.01), and the expression of CD4 and CD8 T lymphocyte CD28 in peripheral blood of ALL children was significantly lower than that of normal children before treatment (P0.01). 3After treatment: the expression of CD4 and CD8 T lymphocyte CTLA-4 in peripheral blood of children with induced sensitive ALL was significantly lower than that before treatment (P0.01), and there was no statistical significance compared with the normal control group (P0.05). 4After treatment: the expression of CD4 and CD8 T lymphocyte CD28 in peripheral blood of children with induced sensitive ALL at complete remission was significantly higher than that before treatment (P0.01), and there was no statistical significance compared with the normal control group (P0.05). 5After treatment: there was no significant change in the expression of CD4 and CD8 T lymphocyte CTLA-4,CD28 in peripheral blood at the time of complete remission of induced insensitive ALL children compared with those before treatment (P0.05). Conclusion: 1in children with B-cell type ALL, the expression of activated stimulatory signal CD28 decreased and the expression of activation-inhibited signal CTLA-4 increased, suggesting that T lymphocytes could not be fully activated and the immune surveillance and clearance function of tumor was decreased. It may be one of the pathogenic factors of ALL. 2Prednisone induced the normal expression of CTLA-4/CD28 when complete remission was achieved in children with sensitive ALL, and the expression of CTLA-4/CD28 was still abnormal in children with insensitive ALL when complete remission was achieved. It is speculated that the inhibition of T lymphocyte activation is the cause and effect of ALL in children. It is possible that leukemic cells produce immune blocking factors in the course of occurrence and development, so that T lymphocytes can not be activated normally, and tumor cells are easy to escape. During the course of 3ALL chemotherapy, attention should be paid to regulating the immune function of T lymphocytes and stimulating the normal activation of T lymphocytes may help to improve the remission rate of treatment of ALL. In addition, the abnormal expression of CTLA-4/CD28 may be one of the indicators of bad prognosis of ALL.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R733.71
[Abstract]:Aim: to investigate the relationship between the expression of CTLA-4/CD28 on peripheral blood T lymphocyte surface and the pathogenesis and treatment outcome of childhood acute lymphoblastic leukemia (ALL). Methods: flow cytometry (FCM) technique was used to detect the surface CTLA-, of peripheral blood T lymphocytes in 27 children with B cell type ALL before and after treatment with VDLD regimen. The complete remission was achieved by VDLD regimen and sustained remission was achieved after CAT consolidation and withdrawal of drugs for 3 weeks. Expression of CD28. Results: (1) before treatment, the expression of CD4 and CD8 T lymphocyte CTLA-4 in peripheral blood of ALL children was significantly higher than that of normal children (P0.01), and the expression of CD4 and CD8 T lymphocyte CD28 in peripheral blood of ALL children was significantly lower than that of normal children before treatment (P0.01). 3After treatment: the expression of CD4 and CD8 T lymphocyte CTLA-4 in peripheral blood of children with induced sensitive ALL was significantly lower than that before treatment (P0.01), and there was no statistical significance compared with the normal control group (P0.05). 4After treatment: the expression of CD4 and CD8 T lymphocyte CD28 in peripheral blood of children with induced sensitive ALL at complete remission was significantly higher than that before treatment (P0.01), and there was no statistical significance compared with the normal control group (P0.05). 5After treatment: there was no significant change in the expression of CD4 and CD8 T lymphocyte CTLA-4,CD28 in peripheral blood at the time of complete remission of induced insensitive ALL children compared with those before treatment (P0.05). Conclusion: 1in children with B-cell type ALL, the expression of activated stimulatory signal CD28 decreased and the expression of activation-inhibited signal CTLA-4 increased, suggesting that T lymphocytes could not be fully activated and the immune surveillance and clearance function of tumor was decreased. It may be one of the pathogenic factors of ALL. 2Prednisone induced the normal expression of CTLA-4/CD28 when complete remission was achieved in children with sensitive ALL, and the expression of CTLA-4/CD28 was still abnormal in children with insensitive ALL when complete remission was achieved. It is speculated that the inhibition of T lymphocyte activation is the cause and effect of ALL in children. It is possible that leukemic cells produce immune blocking factors in the course of occurrence and development, so that T lymphocytes can not be activated normally, and tumor cells are easy to escape. During the course of 3ALL chemotherapy, attention should be paid to regulating the immune function of T lymphocytes and stimulating the normal activation of T lymphocytes may help to improve the remission rate of treatment of ALL. In addition, the abnormal expression of CTLA-4/CD28 may be one of the indicators of bad prognosis of ALL.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R733.71
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