Deleterious effect of HIV-1 plasma viremia on B cell costimulatory function
Deleterious effect of HIV-1 plasma viremia on B cell costimulatory function
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DOI：
10.4049/jimmunol.170.12.5965
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发表时间：
2003-06-15
影响因子：
4.4
通讯作者：
Fauci, AS
中科院分区：
文献类型：
--
作者：
Malaspina, A;Moir, S;Fauci, AS
HIV 感染会导致许多免疫缺陷，包括 B 细胞功能受损。有效的不道德反应需要 B 细胞和 CD4(+) T 细胞之间的双向相互作用，其中关键是活化 B 细胞上表达的 CD80/CD86 与应答 CD4(+) T 细胞上表达的 CD28 之间的相互作用。在本研究中，我们检查了活跃的 HIV 复制对 B 细胞共刺激功能的影响。在一个系统中研究了 B 细胞受体和 CD40 触发后 B 细胞上 CD80/CD86 的诱导以及 CD4(+) T 细胞对活化 B 细胞的反应性，同时将 HIV 感染者的 B 细胞与 HIV 阴性供体的 B 细胞进行比较。与 HIV 病毒血症患者相比，HIV 病毒血症患者的 B 细胞不能有效刺激 CD4(+) T 细胞（通过激活标记物和增殖的诱导来测量）。 CD80/CD86 和 CD28 相互作用在激活 CD4(+) T 细胞中的重要性是显而易见的。添加中和性抗CD86/CD80抗体后正常反应的消除反映了CD4(+) T细胞对HIV病毒血症患者B细胞的反应，而添加外源CD28配体部分恢复了CD4(+) T细胞对HIV病毒血症B细胞的不良反应。患者。 HIV 病毒血症患者中无效的 B 细胞共刺激功能与 B 细胞上 CD80/CD86 表达的低诱导相关。我们的研究结果进一步描绘了 HIV 感染中与同源 B 细胞-CD4(+) T 细胞相互作用相关的缺陷范围，并表明旨在增强 CD28 依赖性共刺激途径的治疗干预措施可能有助于恢复免疫功能。
HIV infection leads to numerous immunologic defects, including impaired B cell function. An effective Immoral response requires bidirectional interactions between B cells and CD4(+) T cells, critical of which are interactions between CD80/CD86 expressed on activated B cells and CD28 expressed on responder CD4(+) T cells. In the present study, we examined the effect of active HIV replication on B cell costimulatory function. Induction of CD80/CD86 on B cells following B cell receptor and CD40 triggering and responsiveness of CD4(+) T cells to activated B cells were investigated in a system where B cells of HIV-infected patients were compared concurrently to B cells of HIV-negative donors. In contrast to HIV-aviremic patients, B cells of HIV-viremic patients were ineffective at stimulating CD4(+) T cells, as measured by the induction of activation markers and proliferation. The importance of interactions of CD80/CD86 and CD28 in activating CD4(+) T cells was clear; the ablation of a normal response following the addition of neutralizing anti-CD86/CD80 Abs mirrored the response of CD4(+) T cells to B cells of HIV-viremic patients, while the addition of exogenous CD28 ligands partially restored the poor CD4(+) T cell response to the B cells of HIV-viremic. patients. Ineffective B cell costimulatory function in HIV-viremic patients was associated with low induction of CD80/CD86 expression on B cells. Our findings further delineate the scope of defects associated with cognate B cell-CD4(+) T cell interactions in HIV infection and suggest that therapeutic interventions designed to enhance CD28-dependent costimulatory pathways may help restore immune functions.