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.
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