HIV-associated multinucleated giant cells in lymphoid tissue of the Waldeyer's ring: A detailed study

HIV-associated multinucleated giant cells in lymphoid tissue of the Waldeyer's ring: A detailed study
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DOI:
10.1038/modpathol.3880237
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发表时间:
2000-12-01
期刊:
影响因子:
7.5
通讯作者:
Verhest, A
Verhest, A
中科院分区:
医学1区
文献类型:
--
作者:
Dargent, JL;Lespagnard, L;Verhest, A

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人类免疫缺陷病毒(HIV)感染患者的Waldeyer环增生淋巴组织偶尔可能含有多核巨细胞(MGCs)。这些细胞,这是无关的任何机会性感染,以前已被证明窝藏大量的艾滋病毒研究进行表征这些MGCs产生了相互矛盾的结果:一些报告提出了巨噬细胞的起源,而其他人支持树突状细胞谱系。本研究的目的是确定一系列来自HIV血清阳性患者的腺样体/扁桃体标本中MGCs的发生率,这些标本没有显示机会性感染的组织学证据,以进一步表征这些细胞的表型,并研究病毒感染在其发病机制中的作用。对21例无机会性感染记录的HIV血清阳性患者的腺样体/扁桃体组织标本进行了仔细检查,以确定是否存在MGCs,并通过针对各种巨噬细胞和DC抗原的抗体在石蜡切片上进行了免疫化学评价。这些抗原包括CD 68、巨噬细胞标志物3A 5、主要组织相容性复合物II类、S-100蛋白、CD 1a和CD 83。还进行了针对CD 21和CD 35以及HIV相关p24抗原的额外免疫染色。最后,分别通过原位杂交和聚合酶链反应分析研究了EB病毒和人疱疹病毒8病毒序列的存在。在14例患者(66.7%)中发现了MGCs,无论性别、年龄、病毒传播方式、CD 4细胞计数、病毒载量或种族如何。这些细胞大多位于扁桃体隐窝的淋巴上皮层,在较小程度上,位于下方淋巴组织的滤泡间区域,这些区域始终表现出滤泡增生的特征。表型上,发现MGCs为CD 68(+)、3A 5(+)、主要组织相容性复合物II类+、S-100蛋白(+/-)、CD 1a(-)、CD 21(-)、CD 35(-)和CD 83(-)。虽然HIV相关的p24蛋白始终存在于这些细胞的细胞质中,但没有表现出Epstein-Barr病毒或人类疱疹病毒8感染的迹象。因此,我们的研究没有显示任何确凿的证据来支持,在增生的淋巴组织的Waldeyer环从HIV血清阳性患者的MGCs起源于树突状细胞。这些细胞的确切性质尚未阐明,但似乎它们只是代表活化的巨噬细胞,在其前体通过腺样体和扁桃体的淋巴上皮区域的循环过程中,这些巨噬细胞被口咽分泌物中存在的HIV感染。
Hyperplastic lymphoid tissues of the Waldeyer's ring in human immunodeficiency virus (HIV)-infected patients may occasionally contain multinucleated giant cells (MGCs). These cells, which are unrelated to any opportunistic Infection, previously have been demonstrated to harbor significant amounts of HIV Studies undertaken to characterize these MGCs have generated conflicting results: some reports suggested a macrophage origin, whereas others supported a dendritic cell lineage. This study was performed to determine the occurrence of MGCs fn a series of adenoid/tonsil specimens from HIV-seropositive patients showing no histological evidence of opportunistic infection in order to further characterize the phenotype of these cells and to investigate the role of a viral infection in their pathogenesis. Adenoid/tonsil tissue specimens from 21 HIV-seropositive patients with no documented opportunistic infection were scrutinized for the presence of MGCs and evaluated immunohistochemically on paraffin sections by antibodies directed against various macrophage and DC antigens. These antigens Included CD68, the macrophage marker 3A5, major histocompatibility complex Class II, S-100 protein, CD1a, and CD83. Additional immunostainings directed at CD21 and CD35 as well as at the HIV-associated p24 antigen were also performed. Finally, the presence of Epstein-Barr virus and human herpesvirus 8 viral sequences was investigated by iia situ hybridization and by polymerase chain reaction analysis, respectively. MGCs were found In 14 patients (66.7%), regardless of gender, age, method of viral transmission, CD4 cell count, viral load, or ethnic group. These cells were mostly localized at the lymphoepithelium layer of the tonsillar crypts and, to a lesser extent, in the interfollicular areas of the underlying lymphoid tissue, which consistently exhibited features of follicular hyperplasia. Phenotypically, MGCs were found to be CD68(+), 3A5(+), major histocompatibility complex Class II+, S-100 protein(+/-) CD1a(-), CD21(-), CD35(-), and CD83(-). Although the HIV-associated p24 protein was consistently present in the cytoplasm of these cells, no sign of Epstein-Barr virus or human herpesvirus 8 infection could be demonstrated. Consequently, our study didn't show any conclusive evidence to support that MGCs in hyperplastic lymphoid tissues of the Waldeyer's ring from HIV-seropositive patients originated from dendritic cells. The definite nature of these cells has yet to be elucidated, but it is plausible that they simply represent activated macrophages that are infected with HIV present in the oropharyngeal secretions during the circulation of their precursor through the lymphoepithelium area of adenoids and tonsils.