Immune responses to recombinant Brugia malayi pepsin inhibitor homolog (Bm-33) in patients with human lymphatic filariaisis

Immune responses to recombinant Brugia malayi pepsin inhibitor homolog (Bm-33) in patients with human lymphatic filariaisis
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DOI:
10.1007/s00436-010-2081-x
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发表时间:
2011-02-01
影响因子:
2
通讯作者:
Narayanan, R. B.
Narayanan, R. B.
中科院分区:
医学3区
文献类型:
--
作者:
Krushna, N. S. A.;Shiny, C.;Narayanan, R. B.

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在人类淋巴丝虫病(微丝虫病(MF)和慢性病理学(CP))以及地方性正常人(EN)患者中研究了重组马来丝虫胃蛋白酶抑制剂同系物(rBm-33)的免疫反应。流式细胞术分析(24小时)显示,与正常人(EN)相比,患者(MF和CP)的CD4(+)T细胞活化,CD69表达增加,CD62L和CD127水平降低。这与 CP 患者中 CD154 表达升高相关,但与 CD28 和 CTLA4 表达升高无关。然而,Bm-33诱导的细胞因子表达谱(IL-1β、IL-12、IL-8、IFN-γ、IL-10和TGF-β)在同一时间点的正常人和患者之间没有表现出任何显着差异。尽管最初在丝虫患者(24小时)中观察到CD4(+)T细胞活化,但淋巴增殖研究(96小时)表明与正常人相比增殖减少,表明前者在长时间抗原暴露后功能失活。这表明 rBm-33 诱导 MF 和 CP 患者早期 T 细胞激活,随后淋巴细胞增殖减少,这可能导致这些个体的免疫抑制。
Immune responses to recombinant Brugia malayi pepsin inhibitor homolog (rBm-33) were investigated in patients with human lymphatic filariasis (microfilaremics (MF) and chronic pathology (CP)) along with endemic normals (EN). Flow cytometric analysis (24 h) revealed CD4(+) T cell activation in patients (MF and CP) compared to normals (EN), with increased expression of CD69 and diminished levels of CD62L and CD127. This was associated with an elevated expression of CD154 but not CD28 and CTLA4 in CP patients. However, Bm-33-induced cytokine expression profile (IL-1 beta, IL-12, IL-8, IFN-gamma, IL-10 and TGF-beta) did not exhibit any significant difference between normals and patients at the same time point. Although CD4(+) T cell activation was observed initially in filarial patients (24 h), lymphoproliferation studies (96 h) suggested diminished proliferation compared to normals, indicating functional inactivation in the former upon prolonged antigen exposure. This indicates that rBm-33 induces an early T cell activation in MF and CP patients followed by a decreased lymphoproliferation that might contribute to immune suppression in these individuals.