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HIV 感染者单核细胞中 MHC II 类抗原加工的保存。

Preserved MHC class II antigen processing in monocytes from HIV-infected individuals.

机构信息

Division of Infectious Diseases and HIV Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.

出版信息

PLoS One. 2010 Mar 3;5(3):e9491. doi: 10.1371/journal.pone.0009491.

Abstract

BACKGROUND

MHC-II restricted CD4+ T cells are dependent on antigen presenting cells (APC) for their activation. APC dysfunction in HIV-infected individuals could accelerate or exacerbate CD4+ T cell dysfunction and may contribute to increased levels of immunodeficiency seen in some patients regardless of their CD4+ T cell numbers. Here we test the hypothesis that APC from HIV-infected individuals have diminished antigen processing and presentation capacity.

METHODOLOGY/PRINCIPAL FINDINGS: Monocytes (MN) were purified by immuno-magnetic bead isolation techniques from HLA-DR1.01+ or DR15.01+ HIV-infected and uninfected individuals. MN were analyzed for surface MHC-II expression and for antigen processing and presentation capacity after overnight incubation with soluble antigen or peptide and HLA-DR matched T cell hybridomas. Surface expression of HLA-DR was 20% reduced (p<0.03) on MN from HIV-infected individuals. In spite of this, there was no significant difference in antigen processing and presentation by MN from 14 HIV-infected donors (8 HLA-DR1.01+ and 6 HLA-DR15.01+) compared to 24 HIV-uninfected HLA-matched subjects.

CONCLUSIONS/SIGNIFICANCE: We demonstrated that MHC class II antigen processing and presentation is preserved in MN from HIV-infected individuals. This further supports the concept that this aspect of APC function does not further contribute to CD4+ T cell dysfunction in HIV disease.

摘要

背景

MHC-II 限制性 CD4+T 细胞的激活依赖于抗原呈递细胞 (APC)。HIV 感染者的 APC 功能障碍可能加速或加剧 CD4+T 细胞功能障碍,并可能导致一些患者的免疫缺陷水平升高,而与 CD4+T 细胞数量无关。在这里,我们检验了这样一个假设,即来自 HIV 感染者的 APC 具有降低的抗原加工和呈递能力。

方法/主要发现:通过免疫磁珠分离技术从 HLA-DR1.01+或 DR15.01+HIV 感染者和未感染者中纯化单核细胞 (MN)。MN 与可溶性抗原或肽孵育过夜后,分析其表面 MHC-II 表达和抗原加工及呈递能力,并与 HLA-DR 匹配的 T 细胞杂交瘤进行比较。来自 HIV 感染者的 MN 表面 HLA-DR 的表达降低了 20%(p<0.03)。尽管如此,与 24 名 HIV 未感染 HLA 匹配的对照者相比,来自 14 名 HIV 感染者(8 名 HLA-DR1.01+和 6 名 HLA-DR15.01+)的 MN 在抗原加工和呈递方面并没有显著差异。

结论/意义:我们证明了 HIV 感染者的 MHC 类 II 抗原加工和呈递在 MN 中得到了保留。这进一步支持了这样一种观点,即 APC 功能的这一方面并没有进一步导致 HIV 疾病中 CD4+T 细胞功能障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff89/2831061/3aa0647ac0cc/pone.0009491.g001.jpg

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