EFFECT OF BRUCELLA ABORTUS ON INTERFERON-GAMMA RELEASE

我们对BA作为人类疫苗开发的载体感兴趣 因为它在刺激人类B细胞时表现为T非依赖的1型抗原 细胞。也就是说，它能够诱导人类B细胞反应(I) T细胞的相对缺失，(Ii)新生儿B细胞和(Iii)B细胞 取自Wiskott-Aldrich综合征患者的细胞(X连锁 免疫缺陷)。这些特性表明BA可能特别 非常适合作为HIV-1衍生蛋白或多肽的载体 引起HIV-1感染者(CD4+受损)的反应 T细胞功能)，以及母亲感染HIV-1的新生儿。近期 有证据表明BA部分依赖于T细胞因子，在 特别是IFNG。在小鼠中，这种诱导IFNG的能力可能与 BA引起某种免疫球蛋白亚类模式的观察 以高滴度的IgG2a为特征。这在以下情况下可能很重要 病毒感染，因为IgG2a对补体和Fc有很高的亲和力 感受器。这个项目的主要目的是调查 BA在人T细胞上的作用，特别是关于IFNG的释放。它是在 有兴趣确定BA是否可以触发CD8+T细胞亚群 因为这些细胞保留在HIV-1感染者体内。刺激 后一类细胞可诱导淋巴因子，从而绕过 对CD4+T细胞的要求。BA被发现能激活人类T细胞以 释放IFNG。此外，CD4+和CD8+人类T细胞都能够 对BA作出反应，分泌IFNG。人T细胞释放干扰素至 IL-2的存在可协同增加BA。这 协同作用可能是由于BA可以增加 人T细胞表面IL-2受体的表达 经流式细胞仪检测证实。

We are interested in BA as a carrier in the development of human vaccines because it behaves as a T-independent type 1 antigen in stimulating human B cells. That is, it is capable of inducing human B cell responses (i) in the relative absence of T cells, (ii) in neonatal human B cells and (iii) in B cells obtained from patients with the Wiskott-Aldrich syndrome (X-linked immunodeficiency). These properties suggest that BA may be particularly well suited as a carrier for HIV-1 derived proteins or peptides in eliciting responses from HIV-1 infected individuals (with compromised CD4+ T cell function) and in neonates who have HIV-1 infected mothers. Recent evidence suggests that BA is partially dependent on T cell factors, in particular IFNG. In mice this ability to induce IFNG is probably related to the observation that BA elicits a certain IgG subclass pattern characterized by high titer IgG2a. This may be important in the context of viral infections because IgG2a has high affinity for complement and Fc receptors. The main purpose of this project was to investigate the effect of BA on human T cells, especially with respect to IFNG release. It was of interest to determine whether BA could trigger the CD8+ T cell subset because these cells are retained in HIV-1 infected individuals. Stimulation of these latter cells may induce lymphokines and thus bypass the requirement for CD4+ T cells. BA was found to activate human T cells to release IFNG. Furthermore, both CD4+ and CD8+ human T cells were capable of responding to BA and secreting IFNG. The IFNG release by human T cells to BA could be synergistically increased in the presence of IL2. This synergism was probably due to the fact that BA could increase the expression of IL-2 receptor on the surface of human T cells, which we demonstrated by flow cytometry.