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oai:ruor.uottawa.ca:10393/382272024-02-23T09:04:09Zcom_10393_242col_10393_11105

Role of Macrophage Subsets in CD8+ T Cell Dysfunction in Chronic HCV Infection Ahmed, Faria Kumar, Ashok HCV Hepatitis C Chronic Infection Immunology Innate Adaptive Macrophages T cells Immune Response Chronic HCV infection causes generalized CD8+T cell impairment, not limited to HCV-specific CD8+ T cells. Infiltrating monocyte-derived macrophages contribute to a micro- environment that could impact CD8+T cells trafficking through the liver. Macrophages can differentiate into pro-inflammatory (M1) and anti-inflammatory (M2a, M2b, and M2c) subsets. Whether macrophage subset generation in chronic HCV infection is altered and if that has a subsequent impact on CD8+T cell functions was not known. I have shown phenotypic alterations in both M1 and M2 macrophages in chronic HCV infection. In particular, M1 from advanced fibrosis patients show increased CD86 expression, reduced spontaneous TNF-α and increased spontaneous IL-10 production. In uninfected controls, co-culturing CD8+T cells with M1 macrophages significantly increased the percentage of CD107a+ and IFN-γ+ CD8+T cells in a contact-dependent manner. Similar autologous co-cultures between M1 and CD8+T cells from patients with chronic HCV infection showed that M1 significantly reduced the percentage of IFN-γ+ CD8+T cells, even though patients displayed elevated IFN-γ+CD8+ T cells at baseline prior to culture. Overall, I demonstrated the altered phenotype of macrophages generated from patients with chronic HCV infection. I also showed the ability of M1 macrophages to induce IFN-γ+CD8+T cells in normal donors and their opposite impact when the cells are derived from chronic HCV infected patients. 2018-10-02T18:17:44Z 2019-10-02T09:00:09Z 2018-10-02 Thesis http://hdl.handle.net/10393/38227 http://dx.doi.org/10.20381/ruor-22481 en application/pdf Université d'Ottawa / University of Ottawa