Identification and enumeration of both dendritic Ia^+ epi-dermal cells (Ia^+DECs) and dendritic Thy-1^+ epidermalcells (Thy-1^+DECa) from various parts of the body wereexamined by using epidermal sheets of C3H/He inbr...Identification and enumeration of both dendritic Ia^+ epi-dermal cells (Ia^+DECs) and dendritic Thy-1^+ epidermalcells (Thy-1^+DECa) from various parts of the body wereexamined by using epidermal sheets of C3H/He inbred miceof different age groups and indirect immunofluorescent tech-nique. A significant decline of both Ia^+DECs and Thy-1^+DECs in the mice of the aged group was demonstrated anddifferent densities and different distribution patterns betweenIa^+DECs and Thy-1^+DECs were obserged. These findingsmay imply that the decline of both Ia^+DECs and Thy-1^+DECs in the aged group may reflect the alterations of im-mune response in aging.展开更多
Objective To observe if VIR576,an 20-mer peptide derived from the C-proximal subfragment of a1-antitrypsin(a1-AT)which inhibits human immunodeficiency virus type 1(HIV-1)entry into the target cells by interacting with...Objective To observe if VIR576,an 20-mer peptide derived from the C-proximal subfragment of a1-antitrypsin(a1-AT)which inhibits human immunodeficiency virus type 1(HIV-1)entry into the target cells by interacting with fusion peptide(FP),can also directly inhibit CD4^(+)T cell activation in vitro.Methods Splenocytes isolated from DO11.10 OVA Tg mice were stimulated with ovalbumin or concanavalin A to test the effects of VIR576 on antigen-specific or non-antigen-specific T cell activation.Both primary CD4^(+)CD25-T cells from DO11.10 mice and CD4^(+)T cell line A2b were activated with specific antigens to evaluate the effects of VIR576.Results VIR576 inhibited antigen-specific splenocyte activation but had no significant effect on non-antigen-specific T-cell activation,which bypassed the crosstalk between the CD3-signaling complex and TCR.We furthermore observed that VIR576 could also down-regulate antigen-specific CD4^(+)T-cell activation.Conclusion Given the high susceptibility of activated CD4^(+)T cells in the mucosa to HIV-1 infection,the inhibitory effects of VIR576 on both HIV entry into the target cells and CD4^(+)T-cell activation suggest the potential of VIR576 as a microbicide for prevention of sexual transmission of HIV.展开更多
目的开发一种共表达PD-L1高亲和受体PD-1(HAPD1)和嵌合抗原受体(CAR)的新型双效CBNK(HAPD1-CARCBNK)细胞,进一步提高肿瘤免疫治疗的疗效。方法首先构建可同时表达高亲和PD-1(HAPD1)的靶向CD19的CAR的双效慢病毒载体,并包装慢病毒感染从...目的开发一种共表达PD-L1高亲和受体PD-1(HAPD1)和嵌合抗原受体(CAR)的新型双效CBNK(HAPD1-CARCBNK)细胞,进一步提高肿瘤免疫治疗的疗效。方法首先构建可同时表达高亲和PD-1(HAPD1)的靶向CD19的CAR的双效慢病毒载体,并包装慢病毒感染从脐血中分离扩增的单个核细胞获得双效脐血CAR-NK细胞。检测分析感染效率、细胞扩增能力、表面标志物表达率;然后通过体外共培养检测细胞在不同效靶比条件下对靶细胞杀伤效率以及不同扩增时期细胞的杀伤效率。最后在免疫缺陷小鼠(24只)体内验证双效CBNK细胞在体内对靶细胞的杀伤能力。结果HAPD1和CAR基因利用慢病毒载体可高效转导至CBNK细胞[(18.63±1.88)%],病毒感染对细胞扩增倍数有一定影响(10.97±2.77 vs 24.84±3.17,P<0.05),但对细胞表面标志物表达没有显著影响(P>0.05);双效NK细胞在效靶比为5:1和10:1时的靶细胞杀伤效力高于普通CARCBNK细胞[(68.38±8.08)%,(79.11±7.42)%vs(49.65±13.60)%,(59.78±9.32)%,P<0.05]。病毒感染后第9~12天双效NK细胞具有最强靶细胞杀伤能力。体内实验进一步证实,双效NK细胞移植28 d后动物白细胞中肿瘤细胞比例低于普通CAR-CBNK细胞移植组[(19.21±3.07)%vs(29.08±3.15)%,P<0.05]。结论本研究成功构建了一种共表达HAPD1和CAR双效CBNK细胞,并在体外和体内实验证实其高效的靶细胞杀伤能力,为肿瘤免疫细胞治疗提供了一个新的有效方案。展开更多
文摘Identification and enumeration of both dendritic Ia^+ epi-dermal cells (Ia^+DECs) and dendritic Thy-1^+ epidermalcells (Thy-1^+DECa) from various parts of the body wereexamined by using epidermal sheets of C3H/He inbred miceof different age groups and indirect immunofluorescent tech-nique. A significant decline of both Ia^+DECs and Thy-1^+DECs in the mice of the aged group was demonstrated anddifferent densities and different distribution patterns betweenIa^+DECs and Thy-1^+DECs were obserged. These findingsmay imply that the decline of both Ia^+DECs and Thy-1^+DECs in the aged group may reflect the alterations of im-mune response in aging.
基金Supported by National Natural Science Foundation of China(30672496 and 30801413)Guangdong Medical Research Grant(A201032)Guangdong International Cooperation Grant(2011B050200006)
文摘Objective To observe if VIR576,an 20-mer peptide derived from the C-proximal subfragment of a1-antitrypsin(a1-AT)which inhibits human immunodeficiency virus type 1(HIV-1)entry into the target cells by interacting with fusion peptide(FP),can also directly inhibit CD4^(+)T cell activation in vitro.Methods Splenocytes isolated from DO11.10 OVA Tg mice were stimulated with ovalbumin or concanavalin A to test the effects of VIR576 on antigen-specific or non-antigen-specific T cell activation.Both primary CD4^(+)CD25-T cells from DO11.10 mice and CD4^(+)T cell line A2b were activated with specific antigens to evaluate the effects of VIR576.Results VIR576 inhibited antigen-specific splenocyte activation but had no significant effect on non-antigen-specific T-cell activation,which bypassed the crosstalk between the CD3-signaling complex and TCR.We furthermore observed that VIR576 could also down-regulate antigen-specific CD4^(+)T-cell activation.Conclusion Given the high susceptibility of activated CD4^(+)T cells in the mucosa to HIV-1 infection,the inhibitory effects of VIR576 on both HIV entry into the target cells and CD4^(+)T-cell activation suggest the potential of VIR576 as a microbicide for prevention of sexual transmission of HIV.
文摘目的开发一种共表达PD-L1高亲和受体PD-1(HAPD1)和嵌合抗原受体(CAR)的新型双效CBNK(HAPD1-CARCBNK)细胞,进一步提高肿瘤免疫治疗的疗效。方法首先构建可同时表达高亲和PD-1(HAPD1)的靶向CD19的CAR的双效慢病毒载体,并包装慢病毒感染从脐血中分离扩增的单个核细胞获得双效脐血CAR-NK细胞。检测分析感染效率、细胞扩增能力、表面标志物表达率;然后通过体外共培养检测细胞在不同效靶比条件下对靶细胞杀伤效率以及不同扩增时期细胞的杀伤效率。最后在免疫缺陷小鼠(24只)体内验证双效CBNK细胞在体内对靶细胞的杀伤能力。结果HAPD1和CAR基因利用慢病毒载体可高效转导至CBNK细胞[(18.63±1.88)%],病毒感染对细胞扩增倍数有一定影响(10.97±2.77 vs 24.84±3.17,P<0.05),但对细胞表面标志物表达没有显著影响(P>0.05);双效NK细胞在效靶比为5:1和10:1时的靶细胞杀伤效力高于普通CARCBNK细胞[(68.38±8.08)%,(79.11±7.42)%vs(49.65±13.60)%,(59.78±9.32)%,P<0.05]。病毒感染后第9~12天双效NK细胞具有最强靶细胞杀伤能力。体内实验进一步证实,双效NK细胞移植28 d后动物白细胞中肿瘤细胞比例低于普通CAR-CBNK细胞移植组[(19.21±3.07)%vs(29.08±3.15)%,P<0.05]。结论本研究成功构建了一种共表达HAPD1和CAR双效CBNK细胞,并在体外和体内实验证实其高效的靶细胞杀伤能力,为肿瘤免疫细胞治疗提供了一个新的有效方案。
