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垂直感染儿童中1型人类免疫缺陷病毒特异性细胞毒性T细胞反应不足

Deficient human immunodeficiency virus type 1-specific cytotoxic T cell responses in vertically infected children.

作者信息

Luzuriaga K, Koup R A, Pikora C A, Brettler D B, Sullivan J L

机构信息

Department of Pediatrics, University of Massachusetts Medical School, Worcester 01605.

出版信息

J Pediatr. 1991 Aug;119(2):230-6. doi: 10.1016/s0022-3476(05)80732-2.

DOI:10.1016/s0022-3476(05)80732-2
PMID:1907319
Abstract

Cytotoxic T lymphocyte (CTL) responses to human immunodeficiency virus type 1 (HIV-1) gag proteins were studied prospectively in 17 children (12 infected) born of mothers with HIV-1 seropositivity and in five pediatric patients with hemophilia infected by transfusion of HIV-1-contaminated factor VIII concentrate. B lymphoblastoid cells infected with vaccinia virus vectors expressing HIV-1 gag gene products were combined with autologous peripheral blood mononuclear cells to detect circulating CTLs. Effector cells were defined by monoclonal antibody-mediated, complement-dependent cytolysis. Circulating HIV-1 gag-specific cytotoxic responses were detectable in 4 of 5 HIV-1-infected pediatric hemophilic patients, and were similar in magnitude to those previously described in adults. In contrast, circulating HIV-1 gag-specific cytolysis was detectible in only 3 of 12 vertically infected children. Depletion data revealed that the majority of detectible gag-specific cytolysis was CD8 T cell-mediated. No apparent relationships between CD4 T cell counts, CD8 T cells counts, or serum p24 antigen levels and CTL responses were seen. Deficient CTL development may, in part, explain the more rapid onset of symptomatic disease following vertical HIV infection.

摘要

前瞻性地研究了17名出生于HIV-1血清阳性母亲的儿童(12名受感染)以及5名因输注受HIV-1污染的VIII因子浓缩物而感染的血友病儿科患者对人类免疫缺陷病毒1型(HIV-1)gag蛋白的细胞毒性T淋巴细胞(CTL)反应。将感染了表达HIV-1 gag基因产物的痘苗病毒载体的B淋巴母细胞与自体外周血单核细胞结合,以检测循环CTL。效应细胞通过单克隆抗体介导的补体依赖性细胞溶解来定义。在5名受HIV-1感染的儿科血友病患者中,有4名检测到循环HIV-1 gag特异性细胞毒性反应,其强度与先前在成人中描述的相似。相比之下,在12名垂直感染的儿童中,只有3名检测到循环HIV-1 gag特异性细胞溶解。去除实验数据显示,大多数可检测到的gag特异性细胞溶解是由CD8 T细胞介导的。未观察到CD4 T细胞计数、CD8 T细胞计数或血清p24抗原水平与CTL反应之间存在明显关系。CTL发育不足可能部分解释了垂直感染HIV后症状性疾病发作更快的原因。

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