EARLY EFFECTS OF SIV INFECTION ON GUT ASSOCIATED LYMPHOID TISSUES

体内的大多数淋巴细胞位于 胃肠道这些淋巴细胞中有很大一部分是 活化的CD4+T细胞是SIV/HIV持续存在的主要靶点 和复制肠道淋巴细胞和/或它们的细胞因子 认为在维护结构和功能方面发挥主要作用 肠粘膜中高尔特成分的改变可能 引起肠道功能的生理性改变，并可能 对被称为艾滋病肠病的综合征负责检查一下 假设，我们正在检查细胞的形态和表型变化。 12只恒河猴感染SIV后的肠道反应 静脉接种SIVmac239，分别于3、7、14、 分别在接种后21天和50天分离淋巴细胞。 外周淋巴结、血液、脾、上皮和板层 空肠、回肠和结肠的固有结构，并进行四色血流分析 CD2、3、4、8、20、25、28、34、38、45RA、56、Leu-8、k 对TCR、HLADR表达的相邻切片进行分析 病毒感染细胞通过原位杂交在14天内pi， CD_4~+淋巴细胞比例显著下降。 与外周淋巴组织相比，肠道组织增多 具有DR+38+和CD56+CD38+表型的CD8+细胞百分比为 7日龄仔猪肠道和外周淋巴组织的观察 原位杂交显示，这些变化与峰值相关 肠道中的病毒载量这一数据表明， SIV感染的胃肠道引起明显的改变 肠道淋巴细胞亚群比例的变化 GALT远比外周淋巴组织明显 最后，肠道淋巴细胞亚群最有可能发生变化。 与肠道功能的显著改变有关，这可能 导致吸收不良、营养不足和/或Inc.减少 肠道对机会性感染的易感性 出版Veazey RS，Lackner AA胃肠道和 艾滋病的发病机制12(增刊)：S35-42,1998年Veazey RS， 首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容 Johnson RP，Desrosiers RC，Lackner AA胃肠道作为一种 CD_4~+淋巴细胞耗竭和病毒复制的主要部位 初级SIV感染科学，180：427-431,1998

The majority of the lymphocytes in the body are located in the gastrointestinal tract A large percentage of these lymphocytes are activated CD4+ T cells and are prime targets for SIV/HIV persistence and replication Intestinal lymphocytes and/or their cytokines are thought to play a major role in maintaining the structure and function of the intestinal mucosa Alterations in the composition of GALT could induce physiologic changes in intestinal function and may be responsible for the syndrome known as AIDS enteropathy To examine this hypotheses, we are examining morphologic and phenotypic changes in the intestinal tract of SIV-infected macaques Twelve rhesus monkeys were intravenously inoculated with SIVmac239 and sacrificed at 3, 7, 14, 21, and 50 days postinoculation Lymphocytes were isolated from peripheral lymph nodes, blood, spleen, and the epithelium and lamina propria of the jejunum, ileum, and colon, and analyzed by 4-color flow cytometry for CD2, 3, 4, 8 , 20, 25, 28, 34, 38, 45RA, 56, Leu-8,k TCR, and HLA-DR expression Adjacent sections were analyzed for virus-infected cells by in situ hybridization Within 14 days pi, profound drops in the proportion of CD4+ lymphocytes were observed in the intestine as compared to peripheral lymphoid tissues Increased percentages of CD8+ cells with DR+38+ and CD56+CD38+ phenotypes were observed both in intestinal and peripheral lymphoid tissue by day 7 pi In situ hybridization revealed that these changes correlated with peak viral load in the intestine This data indicates that infection of the gastrointestinal tract with SIV results in marked changes in the proportions of intestinal lymphocyte subsets Furthermore, changes in the GALT are far more pronounced than in peripheral lymphoid tissue Finally, changes in intestinal lymphocyte subsets are most likely associated with marked alterations in intestinal function which could result in malabsorption, nutritional deficiencies, and/or inc reased susceptibility of the intestine to opportunistic infection Publications Veazey RS, Lackner AA The gastrointestinal tract and the pathogenesis of AIDS AIDS 12(Suppl ) A):S35-42, 1998 Veazey RS, DeMaria MA, Chalifoux LV, Shvetz D, Pauley D, Knight HL, Rosenzweig M, Johnson RP, Desrosiers RC, Lackner AA The gastrointestinal tract as a major site of CD4+ lymphocyte depletion and viral replication in primary SIV infection Science, 180:427-431, 1998