CAJ | 학술논문

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。
인류면역결함병독1형（HIV-1）감염회조성엄중적면역공능손상，제인기CD4＋ T세포불단모손화공능손상외，체액면역응답야수도손상。본연구통과검측HIV-1만성감염자화만성감염치료자외주혈B세포수목화아군비례，이급활화、조망화공자격분자적표체，탐토 HIV-1감염자중B세포손상급항반전록병독치료（ART）대B세포손상적수복작용。결과현시，HIV-1만성감염자외주혈B세포수목현저저우건강대조조，기중미성숙B세포、초시B세포、정식기억B세포화장모세포현저강저，이조직양기억B세포현저증가， ART가회복초시B세포화조직양기억B세포비례，단불능회복정식기억B세포비례。여건강대조조상비， HIV-1감염자미성숙B세포、초시B세포、정식기억B세포화조직양기억B세포중CD38적표체상조；CD95적표체재소유B세포아군중균상조；이Bcl-2재초시B세포、조직양기억B세포화장모세포중적표체현저강저；정식기억B세포화장모세포중PD-1적표체상조；공자격분자CD40재소유B세포아군중적표체강저，이CD70적표체재미성숙B세포이외적아군중균현저하조。ART부능부분수복이상분자적표체。결과표명， HIV-1감염인기B세포급기아군비례이상，B세포표현위과도활화、역조망급여T세포작용수손，ART불능완전수복B세포손상，유효적면역간예책략극대개발。
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 , na?ve B cells , resting memory B cells ,and plasmablasts .However ,tissue-like memory B cells increased significantly .ART could restore the frequencies of na?ve B and tissue-like memory B cells ,but not the resting memory B cells .CD38 was significantly upregulated in immature B cells , na?ve 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 na?ve 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 .