兒童急性淋巴細胞白血病治療前后外周血T細胞表面CTLA-4、CD28的表達
發(fā)布時間：2019-04-27 07:44
【摘要】：目的：探討外周血T淋巴細胞表面CTLA-4/CD28的表達與兒童急性淋巴細胞白血病(ALL)發(fā)病及治療轉(zhuǎn)歸的相關(guān)性。 方法：采用流式細胞儀(FCM)技術(shù)分別檢測27例B細胞型ALL患兒初發(fā)且未治療前、經(jīng)VDLD方案治療達到完全緩解并持續(xù)緩解予CAT鞏固停藥2-3周后外周血T淋巴細胞表面CTLA-、CD28的表達。 結(jié)果：①治療前：ALL患兒外周血CD4+、CD8+T淋巴細胞CTLA-4表達顯著高于正常(P0.01)；②治療前：ALL患兒外周血CD4+、CD8+T淋巴細胞CD28表達顯著低于正常(P0.01)；③治療后：誘導(dǎo)敏感ALL患兒在達到完全緩解時外周血CD4+、CD8+T淋巴細胞CTLA-4的表達顯著低于治療前(P0.01),與正常對照組比較均沒有統(tǒng)計學(xué)意義(P0.05)；④治療后：誘導(dǎo)敏感ALL患兒在達到完全緩解時外周血CD4+、CD8+T淋巴細胞CD28的表達顯著高于治療前(P0.01),與正常對照組比較均沒有統(tǒng)計學(xué)意義(P0.05)；⑤治療后：誘導(dǎo)不敏感ALL患兒在達到完全緩解時外周血CD4+、CD8+T淋巴細胞CTLA-4、CD28的表達與治療前比較均無顯著變化(P0.05)。 結(jié)論：①兒童B細胞型ALL初發(fā)時T細胞活化的刺激信號CD28表達下降,活化抑制信號CTLA-4表達升高,提示T淋巴細胞不能被充分活化,對腫瘤的免疫監(jiān)視與清除功能降低,可能是ALL的發(fā)病因素之一；②強的松誘導(dǎo)敏感ALL患兒在達到完全緩解時CTLA-4/CD28的表達恢復(fù)正常,誘導(dǎo)不敏感ALL患兒在達到完全緩解時CTLA-4/CD28仍然異常表達,推測T淋巴細胞的活化受抑與兒童ALL發(fā)病互為因果,可能白血病細胞在發(fā)生發(fā)展過程中產(chǎn)生免疫封閉因子,使T淋巴細胞不能正�；罨�,腫瘤細胞易于逃逸；③ALL化療過程中注重調(diào)節(jié)T淋巴細胞的免疫功能、刺激T淋巴細胞正�；罨赡苡兄谔岣逜LL的治療緩解率,另外持續(xù)的CTLA-4/CD28的異常表達可能是ALL不良預(yù)后的指標之一
[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.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：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.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R733.71
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