Unraveling the roles of T cells in pulmonary immunology
T cells play an essential role in the immune response to pathogens, serving as both guardians and regulators of host defenses. This thesis dives into the roles of T cells with a focus on infectious diseases and pulmonary immunology, including the effects of immunosuppression. We first introduce the pigtail macaque (PTM) as a novel model for understanding COVID-19, with an emphasis on T cell-mediated immune responses. We show that pulmonary infiltrates were dominated by T cells, including CD4+ T cells that upregulate CD8 and express cytotoxic molecules, as well as virus-targeting T cells that were predominantly CD4+. We then investigate the impact of simian immunodeficiency virus (SIV)-induced immunodeficiency on the progression of COVID-19 disease and the persistence and evolution of SARS-CoV-2. We show that while immunodeficiency induced by SIV appeared to modulate the adaptive response to SARS-CoV-2, as evidenced by a failure to generate neutralizing antibodies or virus-specific T cell responses, it did not alter the overall course of disease or viral kinetics in the PTM model, suggesting that SIV alone may not be sufficient in driving the emergence of novel SARS-CoV-2 variants. These studies prompted us to further explore pulmonary T cells, emphasizing a previously overlooked population of cells in the lung's vascular system. Using intravascular staining (ivs), our findings suggest that pulmonary vascular T cells (ivs+) are a unique population distinct from mere “blood contaminants.” Through flow cytometry and single-cell RNA sequencing, we show that CD8+ T cells are enriched within this group and predominantly exhibit an effector phenotype highlighted by increased Granzyme B (GZMB) expression. These T cells demonstrate a gene expression profile enriched in cell adhesion and extravasation markers, suggesting a unique pulmonary vasculature niche that selects for specific cells. In SIV-infected rhesus macaques (RhM), ivs+ CD8+ T cells showed heightened activity compared to tissue-resident memory CD8+ T cells (TRM). Collectively, this research highlights the role of T cells in infectious disease, particularly within the realm of pulmonary immunology. These findings not only enrich our understanding of T cell biology but also reinforce non-human primates (NHPs) as a valuable animal model in biomedical research, providing crucial insights for the development of novel therapeutics, particularly those that modulate pulmonary T cell responses.