IVIg immune reconstitution treatment alleviates the state of persistent immune activation and suppressed CD4 T cell counts in CVID.
IVIg immune reconstitution treatment alleviates the state of persistent immune activation and suppressed CD4 T cell counts in CVID.
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DOI：
10.1371/journal.pone.0075199
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sandberg JK
中科院分区：
文献类型：
--
作者：
Paquin-Proulx D;Santos BA;Carvalho KI;Toledo-Barros M;Barreto de Oliveira AK;Kokron CM;Kalil J;Moll M;Kallas EG;Sandberg JK
常见变异型免疫缺陷 (CVID) 的特点是 B 细胞功能缺陷、抗体生成受损以及对细菌感染的易感性增加。在这里，我们提出了这样的假设：抗体介导的感染免疫控制不佳可能会导致 T 细胞区室的严重扰动。新诊断的 CVID 患者在开始静脉免疫球蛋白 (IVIg) 治疗之前和之后 6-12 个月进行了采样。初治 CVID 患者表现出 CD4 T 细胞计数和髓样树突状细胞 (mDC) 水平受到抑制，以及 CD8 T 细胞、CD4 T 细胞和不变自然杀伤 T (iNKT) 细胞的高水平免疫激活。 mDC 中共刺激受体 CD80 和 CD83 的表达升高，并与 T 细胞激活相关。 FoxP3+ T 调节 (Treg) 细胞和 iNKT 细胞的水平较低，而表明单核细胞激活的可溶性 CD14 (sCD14) 水平升高。重要的是，用 IVIg 进行免疫重建治疗部分恢复了 CD4 T 细胞和 mDC 区室。治疗还降低了 CD8 T 细胞活化和 mDC 活化水平，而 Treg 细胞和 iNKT 细胞水平仍然较低。因此，体液免疫的原发性缺陷和微生物感染控制受损与细胞介导的免疫的显着病理变化有关。此外，通过 IVIg 输注增强体液免疫的治疗性增强可缓解其中一些缺陷，表明抗体介导的感染免疫控制不良与 T 细胞和 mDC 区室异常的发生之间存在关系。这些发现有助于我们了解原发性免疫缺陷以及 HIV-1 感染引起的获得性免疫缺陷的免疫发病机制。
Common variable immunodeficiency (CVID) is characterized by defective B cell function, impaired antibody production, and increased susceptibility to bacterial infections. Here, we addressed the hypothesis that poor antibody-mediated immune control of infections may result in substantial perturbations in the T cell compartment. Newly diagnosed CVID patients were sampled before, and 6–12 months after, initiation of intravenous immunoglobulin (IVIg) therapy. Treatment-naïve CVID patients displayed suppressed CD4 T cell counts and myeloid dendritic cell (mDC) levels, as well as high levels of immune activation in CD8 T cells, CD4 T cells, and invariant natural killer T (iNKT) cells. Expression of co-stimulatory receptors CD80 and CD83 was elevated in mDCs and correlated with T cell activation. Levels of both FoxP3+ T regulatory (Treg) cells and iNKT cells were low, whereas soluble CD14 (sCD14), indicative of monocyte activation, was elevated. Importantly, immune reconstitution treatment with IVIg partially restored the CD4 T cell and mDC compartments. Treatment furthermore reduced the levels of CD8 T cell activation and mDC activation, whereas levels of Treg cells and iNKT cells remained low. Thus, primary deficiency in humoral immunity with impaired control of microbial infections is associated with significant pathological changes in cell-mediated immunity. Furthermore, therapeutic enhancement of humoral immunity with IVIg infusions alleviates several of these defects, indicating a relationship between poor antibody-mediated immune control of infections and the occurrence of abnormalities in the T cell and mDC compartments. These findings help our understanding of the immunopathogenesis of primary immunodeficiency, as well as acquired immunodeficiency caused by HIV-1 infection.
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