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

摘要

人类免疫缺陷病毒1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细胞损伤及抗反转录病毒治疗（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。结果表明， HIV-1感染引起B细胞及其亚群比例异常，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 1 (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 plasmablasts .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 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 .