Grant: Project Grant - Priority Announcement: HIV/AIDS and STBBI

Approximately 14% of deaths worldwide are due to lung disease. People living with HIV (PLWH) are at higher risk of lung infections and diseases, even when they take effective antiretroviral therapy (ART). Importantly, we showed a higher quantities of HIV reservoirs in the lungs compared to blood despite ART. CD8 T-cells are vital players in immunity via secretion of cytokines and effector molecules which respond to stimuli and cause programmed cell death to eliminate infected cells. Increases in inflammatory CD8 T-cells in the lungs may partially explain why PLWH are more susceptible to lung chronic diseases compared to HIV-uninfected persons. There are also many microbes that normally live inside the lungs which also influence lung immune response. We showed that human lung CD8 T-cells make less effector molecules compared to CD8 T-cells in blood and have less killing capacity. However, T-cells producing IL-17, an inflammatory soluble molecule involved in lungs tissue damages remains understudied. Furthermore, recently it has been found that T-regulatory cells (Tregs) control maintenance of CD8 tissue resident cells. Tregs supress immune response to prevent excessive reactions. We also showed abnormalities in molecules regulating Tregs in lungs compared to blood, during chronic inflammatory diseases like HIV and Simian immunodeficiency virus (SIV). We thus hypothesize that IL-17 producing T-cells affects the lung environment and microbes which, in turn, contribute to pulmonary inflammation within the lungs than the blood. Therefore, we will examine the immunological functions and regulation of lung CD8 T-cells by Tregs, as well as their relationship with the microorganisms which live within the lungs in PLWH and SIV-infected monkeys.