目的：制备乳腺癌患者自体肿瘤特异性细胞毒T淋巴细胞（auto-tumor specificcytotoxicity T lymphocytes，CTLs），观察其对乳腺癌患者骨髓微转移的治疗作用。方法：以CK18、CK19为标志物、应用流式细胞术检测河北医科大学第四医院外一...目的：制备乳腺癌患者自体肿瘤特异性细胞毒T淋巴细胞（auto-tumor specificcytotoxicity T lymphocytes，CTLs），观察其对乳腺癌患者骨髓微转移的治疗作用。方法：以CK18、CK19为标志物、应用流式细胞术检测河北医科大学第四医院外一科2007年3-12月间治疗的82例原发性乳腺癌（Ⅰ～Ⅲ期）术前患者（参加本实验的患者全部知情同意）骨髓微转移状况，将23例术前骨髓微转移阳性的乳腺癌患者随机分为2组：肿瘤特异性CTLs治疗组17例，IL-2治疗对照组6例。术中取治疗组患者腋下淋巴结及外周血体外诱导培养肿瘤特异性CTLs，于术后10—14d回输，观察特异性CTLs对乳腺癌骨髓微转移的治疗效果。结果：本组82例乳腺癌患者中23例（28．05％）骨髓微转移阳性，骨髓微转移的阳性率随临床分期、组织学分级的增加而增高，随ER、PR蛋白表达增强而降低。自乳腺癌患者外周血中成功分离、诱导培养出树突状细胞（dendriticcells，DCs），并经自体肿瘤抗原致敏，与患者腋窝淋巴结来源的淋巴细胞共培养后诱导产生自体肿瘤特异性CTLs。治疗组17例患者经特异性CTLs治疗后，14例转为阴性，转阴率为82．35％；对照组6例中仅1例转为阴性，转阴率为16．67％；肿瘤特异性CTLs的治疗效果显著高于对照治疗（P=0．00028）。结论：成功制备的肿瘤特异性CTLs对乳腺癌骨髓微转移有较好的治疗效果。展开更多
This paper mainly investigates the effect of the lévy jumps on the stochastic HIV infection model with cytotoxic T lymphocytes (CTLs) immune response. First, we prove that there is a unique global positive soluti...This paper mainly investigates the effect of the lévy jumps on the stochastic HIV infection model with cytotoxic T lymphocytes (CTLs) immune response. First, we prove that there is a unique global positive solution in any population dynamics, then we find sufficient conditions for the extinction of the disease. For proofing the persistence in mean, a special Lyapunov function be established, we obtain that if the infected CD4<sup>+</sup> T-cells and virus particles will persistence in mean. Finally, numerical simulations are carried out to illustrate the theoretical results.展开更多
The aim of this study is to find the experimental evidence that the precursor frequency of alloreactive CTLs is proportional to the number of the T-cell epitope specificities. The number of T-cell epitope specificitie...The aim of this study is to find the experimental evidence that the precursor frequency of alloreactive CTLs is proportional to the number of the T-cell epitope specificities. The number of T-cell epitope specificities was manipulated by pulsing different humor of HLA-A2 restricted peptide（s） onto the T2 cells, which acted as stimulating cells to elicit allo-reaction by co-culturing with peripheral blood lymphocytes （PBLs） of HLA-A2 negative individual. Ten HLA-A2 restricted peptides （all were normal cell components ） were synthesized, and cell peptide extract was prepared by frozen and thawed. T2 cells loaded with different number of peptide（s） were co-cultured with PBLs of an HLA-A2 negative individual; the latter were stained with PKH67 in advance. Then the proliferation was monitored with flow cytometry, and the precursor frequency of the effector cells was ＇analyzed by the ModFit Software. After 6 d of culture, no proliferation was observed in the bulk culture of PBL alone, and obvious proliferation took place when PBLs of the HLA-A2 negative were co-cultured with T2 cells loaded with or without loading peptide（ s）. The precursor frequency of the alloreactive CTLs was 0.052 819 for co-culture with T2 cells loaded without peptide; however it was 0. 030 429 for T2 cells with EBV/LMP2A and 0. 030 528 for T2 cells loaded with a single autogeneic peptide, and increased up to 0. 144 942 for T2 cells loaded with 10 autogeneic peptides; the precursor frequency was 0. 203 649 when co-cultured with T2 cells loaded with miscellaneous peptides extracted from the cytoplasm of T2 cells. This study reveals that the precursor frequency of alloreactive CTLs is proportional to the number of T-cell epitope specificities, and independent of the density of the allogeneic HLA Class Ⅰ molecule. Our findings support the hypothesis that the alloreactive T cell populations comprise miscellaneous T cell clones; each is specific to corresponding pMHC. The novel constellation of peptides presented by allogeneic MHC molecules makes thousands of different epitopes, which account for the exceptional high precursor frequency of alloreactive T cells.展开更多
文摘目的：制备乳腺癌患者自体肿瘤特异性细胞毒T淋巴细胞（auto-tumor specificcytotoxicity T lymphocytes，CTLs），观察其对乳腺癌患者骨髓微转移的治疗作用。方法：以CK18、CK19为标志物、应用流式细胞术检测河北医科大学第四医院外一科2007年3-12月间治疗的82例原发性乳腺癌（Ⅰ～Ⅲ期）术前患者（参加本实验的患者全部知情同意）骨髓微转移状况，将23例术前骨髓微转移阳性的乳腺癌患者随机分为2组：肿瘤特异性CTLs治疗组17例，IL-2治疗对照组6例。术中取治疗组患者腋下淋巴结及外周血体外诱导培养肿瘤特异性CTLs，于术后10—14d回输，观察特异性CTLs对乳腺癌骨髓微转移的治疗效果。结果：本组82例乳腺癌患者中23例（28．05％）骨髓微转移阳性，骨髓微转移的阳性率随临床分期、组织学分级的增加而增高，随ER、PR蛋白表达增强而降低。自乳腺癌患者外周血中成功分离、诱导培养出树突状细胞（dendriticcells，DCs），并经自体肿瘤抗原致敏，与患者腋窝淋巴结来源的淋巴细胞共培养后诱导产生自体肿瘤特异性CTLs。治疗组17例患者经特异性CTLs治疗后，14例转为阴性，转阴率为82．35％；对照组6例中仅1例转为阴性，转阴率为16．67％；肿瘤特异性CTLs的治疗效果显著高于对照治疗（P=0．00028）。结论：成功制备的肿瘤特异性CTLs对乳腺癌骨髓微转移有较好的治疗效果。
文摘This paper mainly investigates the effect of the lévy jumps on the stochastic HIV infection model with cytotoxic T lymphocytes (CTLs) immune response. First, we prove that there is a unique global positive solution in any population dynamics, then we find sufficient conditions for the extinction of the disease. For proofing the persistence in mean, a special Lyapunov function be established, we obtain that if the infected CD4<sup>+</sup> T-cells and virus particles will persistence in mean. Finally, numerical simulations are carried out to illustrate the theoretical results.
基金The work was supported by the grants from the National Natural Science Foundation of China(No.30271201)the Major State Basic Research Development Program of China(No.2001C510008).
文摘The aim of this study is to find the experimental evidence that the precursor frequency of alloreactive CTLs is proportional to the number of the T-cell epitope specificities. The number of T-cell epitope specificities was manipulated by pulsing different humor of HLA-A2 restricted peptide（s） onto the T2 cells, which acted as stimulating cells to elicit allo-reaction by co-culturing with peripheral blood lymphocytes （PBLs） of HLA-A2 negative individual. Ten HLA-A2 restricted peptides （all were normal cell components ） were synthesized, and cell peptide extract was prepared by frozen and thawed. T2 cells loaded with different number of peptide（s） were co-cultured with PBLs of an HLA-A2 negative individual; the latter were stained with PKH67 in advance. Then the proliferation was monitored with flow cytometry, and the precursor frequency of the effector cells was ＇analyzed by the ModFit Software. After 6 d of culture, no proliferation was observed in the bulk culture of PBL alone, and obvious proliferation took place when PBLs of the HLA-A2 negative were co-cultured with T2 cells loaded with or without loading peptide（ s）. The precursor frequency of the alloreactive CTLs was 0.052 819 for co-culture with T2 cells loaded without peptide; however it was 0. 030 429 for T2 cells with EBV/LMP2A and 0. 030 528 for T2 cells loaded with a single autogeneic peptide, and increased up to 0. 144 942 for T2 cells loaded with 10 autogeneic peptides; the precursor frequency was 0. 203 649 when co-cultured with T2 cells loaded with miscellaneous peptides extracted from the cytoplasm of T2 cells. This study reveals that the precursor frequency of alloreactive CTLs is proportional to the number of T-cell epitope specificities, and independent of the density of the allogeneic HLA Class Ⅰ molecule. Our findings support the hypothesis that the alloreactive T cell populations comprise miscellaneous T cell clones; each is specific to corresponding pMHC. The novel constellation of peptides presented by allogeneic MHC molecules makes thousands of different epitopes, which account for the exceptional high precursor frequency of alloreactive T cells.
