
人类免疫缺陷病毒1型慢性感染者B细胞表型分析及抗反转录病毒治疗的修复作用
闫静静1,仇超1,2,3,李亮助1,2,邱趁丽1,傅卫辉1,2,孙俊1,徐建青1,2,3,张晓燕1,2,3
微生物与感染 ›› 2013, Vol. 8 ›› Issue (3) : 144-152.
人类免疫缺陷病毒1型慢性感染者B细胞表型分析及抗反转录病毒治疗的修复作用
Analysis of B cell phenotype and the restoration of antiretroviral therapy in chronic human immunodeficiency virus type 1 infection
人类免疫缺陷病毒Ⅰ型(HIV-1)感染会造成严重的免疫功能损伤,除引起CD4+ T细胞不断耗损和功能损伤外,体液免疫应答也受到损伤。本研究通过检测HIV-1慢性感染者和慢性感染治疗者外周血B细胞数目和亚群比例,以及活化、凋亡和共刺激分子的表达,探讨HIV-1感染者中B细胞损伤及抗病毒治疗(ART)对B细胞损伤的修复作用。结果显示,HIV-1慢性感染者外周血B细胞数目显著低于健康对照组,其中未成熟B细胞、初始B细胞、静息记忆B细胞和浆母细胞显著降低,而组织样记忆B细胞显著增加,ART可恢复初始B细胞和组织样记忆B细胞比例,但不能恢复静息记忆B细胞比例。与健康对照组相比,HIV-1感染者未成熟B细胞、初始B细胞、静息记忆B细胞和组织样记忆B细胞中CD38的表达上调;CD95的表达在所有B细胞亚群中均上调;而Bcl-2在初始B细胞、组织样记忆B细胞和浆母细胞中的表达显著降低;静息记忆B细胞和浆母细胞中PD-1的表达上调;共刺激分子CD40在所有B细胞亚群中的表达强度降低,而CD70的表达在未成熟B细胞以外的亚群中均显著下调;ART仅能部分修复以上分子的表达。以上结果表明,HIV-1感染引起B细胞及其亚群比例的异常,B细胞表现为过度活化、易凋亡及与T细胞作用受损,ART不能完全修复B细胞损伤,有效的免疫干预策略亟待开发。
Human immunodeficiency virus type I (HIV-1) infection leads to severe immune dysfunction. In addition to the progressive depletion and dysfunction of CD4+ T cells, HIV-1 infection also leads to extensive defects in the humoral arm of the immune system. This study aimed to describe the distribution of B cell subpopulations and profiles of activated, apoptosis-associated and costimulatory molecules in each subpopulation. The results showed that the peripheral blood B cell counts in HIV-1 infected patients were significantly lower than that in the healthy controls, but could be restored by antiretroviral therapy (ART). The decline of B cell counts was manifested by the decrease of immature B cells, Naïve B cells, resting memory B cells, and plasmablast. However, tissue-like memory B cells increased significantly. ART could restore the frequencies of naïve B and tissue-like memory B cells, but not the resting memory B cells. CD38 was significantly upregulated in immature B cells, naïve B cells, resting memory B cells and tissue-like memory B cells in HIV-1-infected patients, when compared to healthy controls. All subpopulations showed higher expression of CD95, and naïve B cells, tissue-like memory B cells and plasmablasts exhibited decreased levels of Bcl-2. PD-1 was elevated only in the resting memory cells and plasmablasts. The mean fluorescent intensity of CD40 was diminished in all B cell subpopulations, whereas CD70 decreased in all subpopulations except immature B cells. However, ART could only partially restore the altered expression of the mentioned molecules. These results suggest that HIV-1 infection leads to perturbation of B cell subpopulations, and B cell subpopulations display hyperactivation, susceptibility to apoptosis and impaired interaction with T cells. These alterations could only be restored partially by successful ART, therefore, effective immune intervention strategies should be required.
人免疫缺陷病毒Ⅰ型 / B细胞 / 表型 / 抗反转录病毒治疗
Human immunodeficiency virus type 1 / B cell / Phenotype / Antiretroviral therapy
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