目的:观察慢性HIV-1感染者中CD4+和CD8+T淋巴细胞上BTLA(B and T lymphocyte attenuator,CD272)分子的表达及临床意义。方法:采集34例慢性HIV-1感染者和15例健康人的外周血,分离外周血单个核细胞,用间接免疫荧光染色方法标记并用流式细...目的:观察慢性HIV-1感染者中CD4+和CD8+T淋巴细胞上BTLA(B and T lymphocyte attenuator,CD272)分子的表达及临床意义。方法:采集34例慢性HIV-1感染者和15例健康人的外周血,分离外周血单个核细胞,用间接免疫荧光染色方法标记并用流式细胞术检测T淋巴细胞上BTLA表达的百分比及平均荧光强度,并将BTLA的表达水平与患者CD4+T淋巴细胞计数和病毒载量做相关性分析。结果:与健康对照相比,HIV-1慢性感染者中CD4+和CD8+T细胞上的BTLA表达均明显下降,且BTLA的下降在各组HIV-1慢性感染者中也有明显差异,随着疾病进展,BTLA表达进行性下降。CD4+T细胞上BTLA表达比率与平均荧光强度均与CD4+T淋巴细胞计数呈明显正相关,而与病毒载量呈负相关。结论:在慢性HIV-1感染中,随着疾病进展,BTLA的进行性下降可能是机体活化和抑制信号失衡、导致免疫系统广泛活化的重要因素,恢复BTLA抑制信号的强度可能是治疗HIV感染的新策略。展开更多
Multiple sclerosis is an autoimmune disease characterised by a chronic inflammation within the central nervous system. In the last ten years, studies on multiple sclerosis have been concentrated on the discovery of ne...Multiple sclerosis is an autoimmune disease characterised by a chronic inflammation within the central nervous system. In the last ten years, studies on multiple sclerosis have been concentrated on the discovery of new biomarkers of disease and potential therapeutic targets. In chronic infection or in cancer, the immune system response is faulty and maintained in a condition defined as T-cell exhaustion induced by expression of co-inhibitory receptors. The PD-1/PDL-1 pathway is demonstrated to be the main one responsible for promoting T-cell exhaustion, and immunotherapies targeting PD-1 or PDL-1 have shown beneficial clinical outcomes in several tumours and chronic diseases. Contrarily, transcriptional T-cell exhaustion signature and high expression of co-inhibitor receptor PD-1 are associated with favourable prognosis in multiple sclerosis and other autoimmune diseases. Several studies have clearly demonstrated PD-1 has a dual role in immune self-tolerance: to constrain autoreactive T cells in anergic condition and to protect the tissue from the damage caused by the activation of endogenous autoreactive T cells. Consequently, immune checkpoint inhibitor therapies that target inhibitory receptors in cancer cause an exacerbation of autoimmune diseases. This review describes the roles of the PD-1/ PDL-1 pathway in cancer and autoimmune diseases, especially in multiple sclerosis, and how manipulating PD-1 can be a therapeutic approach in multiple sclerosis.展开更多
文摘目的:观察慢性HIV-1感染者中CD4+和CD8+T淋巴细胞上BTLA(B and T lymphocyte attenuator,CD272)分子的表达及临床意义。方法:采集34例慢性HIV-1感染者和15例健康人的外周血,分离外周血单个核细胞,用间接免疫荧光染色方法标记并用流式细胞术检测T淋巴细胞上BTLA表达的百分比及平均荧光强度,并将BTLA的表达水平与患者CD4+T淋巴细胞计数和病毒载量做相关性分析。结果:与健康对照相比,HIV-1慢性感染者中CD4+和CD8+T细胞上的BTLA表达均明显下降,且BTLA的下降在各组HIV-1慢性感染者中也有明显差异,随着疾病进展,BTLA表达进行性下降。CD4+T细胞上BTLA表达比率与平均荧光强度均与CD4+T淋巴细胞计数呈明显正相关,而与病毒载量呈负相关。结论:在慢性HIV-1感染中,随着疾病进展,BTLA的进行性下降可能是机体活化和抑制信号失衡、导致免疫系统广泛活化的重要因素,恢复BTLA抑制信号的强度可能是治疗HIV感染的新策略。
基金Fondazione Italiana Sclerosi Multipla(ref.2015/R/16 to PM)by Elena Pecci research project and Fondazione Careggi Onlus.
文摘Multiple sclerosis is an autoimmune disease characterised by a chronic inflammation within the central nervous system. In the last ten years, studies on multiple sclerosis have been concentrated on the discovery of new biomarkers of disease and potential therapeutic targets. In chronic infection or in cancer, the immune system response is faulty and maintained in a condition defined as T-cell exhaustion induced by expression of co-inhibitory receptors. The PD-1/PDL-1 pathway is demonstrated to be the main one responsible for promoting T-cell exhaustion, and immunotherapies targeting PD-1 or PDL-1 have shown beneficial clinical outcomes in several tumours and chronic diseases. Contrarily, transcriptional T-cell exhaustion signature and high expression of co-inhibitor receptor PD-1 are associated with favourable prognosis in multiple sclerosis and other autoimmune diseases. Several studies have clearly demonstrated PD-1 has a dual role in immune self-tolerance: to constrain autoreactive T cells in anergic condition and to protect the tissue from the damage caused by the activation of endogenous autoreactive T cells. Consequently, immune checkpoint inhibitor therapies that target inhibitory receptors in cancer cause an exacerbation of autoimmune diseases. This review describes the roles of the PD-1/ PDL-1 pathway in cancer and autoimmune diseases, especially in multiple sclerosis, and how manipulating PD-1 can be a therapeutic approach in multiple sclerosis.
