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在淋巴滤泡和生殖上皮中存在的CD8 MHC I类四聚体SIV特异性T细胞的局部群体。

Localized populations of CD8 MHC class I tetramer SIV-specific T cells in lymphoid follicles and genital epithelium.

作者信息

Hong Jung Joo, Reynolds Matthew R, Mattila Teresa L, Hage Aaron, Watkins David I, Miller Christopher J, Skinner Pamela J

机构信息

Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, Minnesota, United States of America.

出版信息

PLoS One. 2009;4(1):e4131. doi: 10.1371/journal.pone.0004131. Epub 2009 Jan 5.

Abstract

CD8 T cells play an important role in controlling viral infections. We investigated the in situ localization of simian immunodeficiency virus (SIV)-specific T cells in lymph and genital tissues from SIV-infected macaques using MHC-class I tetramers. The majority of tetramer-binding cells localized in T cell zones and were CD8(+). Curiously, small subpopulations of tetramer-binding cells that had little to no surface CD8 were detected in situ both early and late post-infection, and in both vaginally and rectally inoculated macaques. These tetramer(+)CD8(low/-) cells were more often localized in apparent B cell follicles relative to T cell zones and more often found near or within the genital epithelium than the submucosa. Cells analyzed by flow cytometry showed similar populations of cells. Further immunohistological characterization revealed small populations of tetramer(+)CD20(-) cells inside B cell follicles and that tetramer(+) cells did not stain with gammadelta-TCR nor CD4 antibodies. Negative control tetramer staining indicated that tetramer(+)CD8(low/-) cells were not likely NK cells non-specifically binding to MHC tetramers. These findings have important implications for SIV-specific and other antigen-specific T cell function in these specific tissue locations, and suggest a model in which antigen-specific CD8+ T cells down modulate CD8 upon entering B cell follicles or the epithelial layer of tissues, or alternatively a model in which only antigen-specific CD8 T cells that down-modulate CD8 can enter B cell follicles or the epithelium.

摘要

CD8 T细胞在控制病毒感染中发挥着重要作用。我们使用MHC-I类四聚体研究了感染猴免疫缺陷病毒(SIV)的猕猴的淋巴和生殖组织中SIV特异性T细胞的原位定位。大多数四聚体结合细胞定位于T细胞区,且为CD8(+)。奇怪的是,在感染后的早期和晚期,以及经阴道和直肠接种的猕猴中,均在原位检测到少量几乎没有表面CD8的四聚体结合细胞亚群。相对于T细胞区,这些四聚体(+)CD8(low/-)细胞更常定位于明显的B细胞滤泡中,并且相对于黏膜下层,在生殖上皮附近或内部更常被发现。通过流式细胞术分析的细胞显示出类似的细胞群体。进一步的免疫组织学特征揭示了B细胞滤泡内少量的四聚体(+)CD20(-)细胞,并且四聚体(+)细胞不与γδ-TCR或CD4抗体染色。阴性对照四聚体染色表明,四聚体(+)CD8(low/-)细胞不太可能是与MHC四聚体非特异性结合的NK细胞。这些发现对于这些特定组织部位中SIV特异性和其他抗原特异性T细胞功能具有重要意义,并提示了一种模型,即抗原特异性CD8+ T细胞在进入B细胞滤泡或组织上皮层时下调CD8,或者另一种模型,即只有下调CD8的抗原特异性CD8 T细胞才能进入B细胞滤泡或上皮。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9e3/2607009/de10857e6a04/pone.0004131.g001.jpg

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