ORAL IMMUNE DYSFUNCTION AND CANDIDIASIS IN HIV INFECTION

描述：(改编自申请者摘要)保护性T细胞介导 (CMI)在口腔粘膜的机制尚不清楚。口咽部 念珠菌病(OPC)是人类免疫缺陷病毒感染最常见的口腔疾病。 在发展为艾滋病的过程中出现免疫抑制的第一个临床迹象。它 然而，口腔粘膜中发生了什么免疫学事件尚不清楚。 促进白色念珠菌从共生菌向病原菌的转化 最终走向OPC的发展。临床和实验室 研究表明，CMI(T细胞，细胞因子)是主要宿主 粘膜表面对白色念珠菌的防御机制。预赛 PI的数据和临床观察表明，虽然两者 全身和局部免疫很重要，它们可能在一定程度上发挥作用 独立自主。私家侦探假设，患有 晚期HIV感染导致OPC和其他口腔疾病 口腔正常保护性脑缺血的特异性改变/功能障碍(S) 可能与全身性CMI相关或不相关的粘膜。为了测试这一点 假设，他将专注于城市患者队列中患有OPC的个体 具有相当大的年龄、性别和种族多样性的艾滋病毒+个人 路易斯安那州立大学医学中心的HIV门诊计划(HOP)，并执行 有三个具体目标的横断面病例对照研究。这个 申请者将1)描述HIV+患者口腔中的CD4+/CD8+淋巴细胞的特征 患有和不患有OPC的个人以及艾滋病毒患者--通过 口腔活检组织的分子和免疫学分析；2)表征 口服分泌Th相关免疫分子(即细胞因子、抗体) 通过对唾液和活检样本的分析，在每一组患者中；以及 3)将粘膜免疫图谱与定量和定性相关联 两种HIV相关病毒的聚合酶链式反应测定病毒载量 口腔中的基因(Gag和Pro)。收集到的关于口述的数据 空洞将与全身隔室中的水平(血液， 体外刺激的血浆和血淋巴细胞培养上清液中 念珠菌抗原)。这个项目的长期目标是 了解口腔粘膜中的CMI，以确定免疫事件/条件 与HIV+个体对OPC的易感性有关，并与 制定基于免疫学的策略以增强抵抗力/保护力 在艾滋病毒感染期间对抗口腔病原体。

DESCRIPTION: (Adapted from applicant's abstract) Protective T cell-mediated (CMI) mechanisms at the oral mucosa are poorly understood. Oropharyngeal candidiasis (OPC) is the most common oral manisfestation of HIV infection and first clinical sign of immunosuppression during progression to AIDS. It is unclear, however, what immunological events take place in the oral mucosa to promote the conversion of Candida albicans from commensal to pathogen and ultimately to the development of OPC. Clinical and laboratory investigations suggest that CMI (T cells, cytokines) is the predominant host defense mechanism against C. albicans at mucosal surfaces. The preliminary data of the PI together with clinical observations indicate that while both systemic and local immunity is important, they may function with some level of independence. The PI hypothesizes that individuals suffering from advanced HIV infection acquire OPC and other oral diseases as a result of specific changes/dysfunction(s) in the normal protective CMI at the oral mucosa that may or may not correlate with systemic CMI. To test this hypothesis, he will focus on individuals with OPC in an urban patient cohort of HIV+ individuals with considerable age, gender, and racial diversity in the HIV Outpatient Program (HOP) at LSU Medical Center and perform a cross-sectional, case-controlled study with three Specific Aims. The applicant will 1) characterize the oral CD4+/CD8+ lymphocyte profile in HIV+ individuals with and without OPC and in HIV- individuals through the molecular and immunological analysis of oral biopsy tissue; 2) characterize the orally secreted Th-related immune molecules (ie., cytokines, antibodies) in each patient group through the analysis of saliva and biopsy samples; and 3) correlate the mucosal immune profile with quantitative and qualitative measurements of viral load determined by PCR of two HIV-associated viral genes (gag and pro) in the oral cavity. Data gathered relative to the oral cavity will be correlated to levels in the systemic compartment (blood, plasma and in the supernatants of blood lymphocytes stimulated in vitro with Candida antigens). The long-term goals of this project are to better understand CMI in the oral mucosa, to define immunological events/conditions associated with the susceptibility of HIV+ individuals to OPC, and to develop immunological based strategies to enhance resistance/protection against oral pathogens during HIV infection.