MUCOSAL AND SERUM IGA SYSTEMS IN AIDS

粘膜免疫系统在HIV感染发病机制中的重要性 及其在生产保护性疫苗中的潜在意义 直到最近才被承认。很明显，感染这种病毒 病毒深刻地影响粘膜免疫系统。特别 值得注意的是对胃肠道的影响。本 申请建议扩大正在进行的研究，旨在确定 HIV感染中人类伊加系统的参数。为此将 通过充分表征分泌型伊加抗HIV的功能， 从血清反应阳性妇女的初乳中分离的抗体， 伊加抗体在介导粘膜感染中的作用 上皮细胞和研究伊加功能，在体内使用严重的 用人细胞重建的联合免疫缺陷（SCID）小鼠， 感染了艾滋病病毒提出了以下具体目标：1。 确定伊加抗体增强HIV感染的潜力 通过多聚免疫球蛋白受体 （分泌成分，SC）或碳水化合物介导的相互作用 （伊加分子的半乳糖和细胞表面半乳糖基转移酶）， 使用已知的胃肠道来源的HT 29和T84人细胞系 表达SC和半乳糖基转移酶;阐明联合国的作用 细胞因子在增强HIV感染和摄取中的作用 胃肠道上皮细胞系; 3.表征 分离自HIV感染者的分泌型伊加抗HIV抗体的功能 艾滋病毒阳性母亲的初乳。

The importance of the mucosal immune system in pathogenesis HIV infection and its potential significance in the production of protective vaccines has only recently been acknowledged. It is clear that infection with this virus profoundly affects the mucosal immune system. Particularly noteworthy is the effect on the gastrointestinal tract. The present application proposes to extend ongoing studies aimed at defining parameters of the human IgA system in HIV infection. This will be done by fully characterizing the functions of secretory IgA anti-HIV antibodies isolated from the colostrum of seropositive women, determining the role(s) of IgA antibodies in mediating infection of mucosal epithelial cells and by studying IgA function in vivo using severe combined immunodeficient (SCID) mice reconstituted with human cells and infected with HIV. The following specific aims are proposed: 1. Determination of the potential of IgA antibodies to enhance HIV infection of epithelial cells via either the polymeric immunoglobulin receptor (secretory compontent, SC) or by carbohydrate-mediated interactions (galactose of IgA molecules and cell surface galactosyltransferase), using the HT29 and T84 human cell lines of gastrointestinal origin known to express SC and galactosyltransferase; 2. Elucidation of the role of cytokines in enhancement of infection and uptake of HIV by gastrointestinal epithelial cell lines; 3. Characterization of the function(s) of secretory IgA anti-HIV antibodies isolated from the colostrum of HIV-positive mothers.