Candida albicans-specific mucosal CD4+ T cell clones

描述(由申请人提供)： 白色念珠菌是一种共生菌，它定植于皮肤和粘膜表面，包括口腔。有机体在粘膜和口腔器械上形成生物膜，例如假牙，通常与细菌结合。这种微生物也是这些表面的机会性感染以及播散性疾病的病原体。在最容易受到口腔感染的人中，HIV+患者的CD4+T细胞正在下降。这种淋巴细胞群的丧失与疾病之间的相关性暗示了CD4+T细胞在保护健康个体免受疾病侵袭中的作用。在小鼠感染模型中，CD4+T细胞也与易感性有关。虽然T辅助1型细胞介导免疫(CMI)在系统和粘膜感染的保护和恢复中有一定的作用，但也清楚地表明，粘膜和系统免疫反应具有区隔的成分。强调这一点的是艾滋病患者对口腔粘膜疾病的易感性，而不是全身疾病。口腔粘膜中的T细胞与外周血中T细胞的分布不同。近年来，T细胞克隆已经成为识别刺激CMI反应的特定抗原及其表位的有用工具。然而，这些方案的应用已经应用于外周循环的淋巴细胞，而不是那些在口腔病原体反应中起重要作用的口腔粘膜的淋巴细胞。这项建议的目标是建立程序，分离来自白色念珠菌定植的小鼠口腔粘膜T细胞群的CD4+T细胞克隆。该方法的成功开发具有特定的应用价值，将为后续研究口腔白色念珠菌的宿主反应和控制提供重要的工具。一种成功的方案还将被更广泛地应用于研究粘膜对正常口腔菌群组分和口腔感染剂的反应。

DESCRIPTION (provided by applicant): Candida albicans is a commensal that colonizes skin and mucosal surfaces including the oral cavity. The organism forms biofilms on mucosa and oral devices, e.g. dentures, generally in association with bacteria. The organism is also an agent of opportunistic infection of these surfaces as well as disseminated disease. Among individuals that are most susceptible to oral infection are HIV+ patients who have declining CD4+ T cells. The correlation between loss of this lymphocyte population and disease implicates CD4+ T cells in protection of the healthy individual from disease. CD4+ T cells have also been implicated in susceptibility in murine models of infection. While T-helper 1 type cell-mediated immunity (CMI) has been implicated in protection and recovery from both systemic and mucosal infection, it is also clear that mucosal and systemic immune response has elements of compartmentalization. This is emphasized by the susceptibility of the AIDS patient to oral mucosal but not systemic disease. The profile of T cells in the oral mucosa differs from that of peripheral blood. In recent years, T cells clones have been a useful tool to identify the specific antigens and their epitopes that stimulate the CMI response. However, the application of these protocols has been applied to lymphocytes of peripheral circulation and not those of the oral mucosa that are important in the response to oral pathogens. The goal of this proposal is to establish procedures for isolating CD4+ T cell clones that are derived from the T cell population of the oral mucosa in mice colonized with C. albicans. The successful development of this protocol has specific application that will provide a major tool for subsequent studies of host response and control of oral C. albicans. A successful protocol will also have more widespread application to study the mucosal response to components of the normal oral flora and agents of oral infection.