ORAL IMMUNE DYSFUNCTION AND CANDIDIASIS IN HIV INFECTION

描述：（改编自申请人摘要）保护性T细胞介导的 (CMI)口腔粘膜的机制知之甚少。 口咽 念珠菌病（OPC）是HIV感染最常见的口腔表现 和艾滋病进展过程中免疫抑制的第一个临床体征。 它 然而，尚不清楚口腔粘膜中发生了什么免疫学事件 促进白色念珠菌从真菌向病原体的转化， 最后是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 防御机制粘膜表面有白色念珠菌。 初步 PI数据和临床观察结果表明， 全身和局部免疫是重要的，它们可以在一定水平上发挥作用， 独立性。 PI假设患有 晚期HIV感染者由于以下原因而获得OPC和其他口腔疾病： 口腔正常保护性CMI的特定变化/功能障碍 可能与或可能与系统性CMI无关的粘膜。 为了验证这一 假设，他将重点放在个人与OPC在城市患者队列 艾滋病毒+个体具有相当大的年龄，性别和种族多样性， 艾滋病毒门诊计划（HOP）在路易斯安那州立大学医疗中心，并执行一项 具有三个特定目的的横断面病例对照研究。 的 申请人将1）描述HIV+患者的口服CD 4 +/CD 8+淋巴细胞特征 有和没有OPC和艾滋病毒的个人-通过 口腔活检组织的分子和免疫学分析; 2）表征 口腔分泌的Th相关免疫分子（即，细胞因子、抗体） 通过分析唾液和活检样本在每个患者组中进行;以及 3)将粘膜免疫谱与定量和定性 通过PCR测定两种HIV相关病毒的病毒载量 基因（gag和pro）在口腔中。 收集的数据与口服 空腔将与系统隔室（血液， 血浆和体外刺激的血淋巴细胞上清液中 念珠菌抗原）。 该项目的长期目标是更好地 了解口腔粘膜中的CMI，以定义免疫学事件/状况 与HIV+个体对OPC的易感性相关， 制定基于免疫学的策略，以增强抵抗力/保护力 在HIV感染期间抵抗口腔病原体。

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.