{"id":{"repo_id":"ottawa-retro","oai_identifier":"oai:ruor.uottawa.ca:10393/38227"},"canonical_url":"https://search.dev.ndltd.org/etd/ottawa-retro/oai:ruor.uottawa.ca:10393/38227","repository":{"repo_id":"ottawa-retro","name":"University of Ottawa","base_url":"https://ruor.uottawa.ca/server/oai/request"},"display":{"title":"Role of Macrophage Subsets in CD8+ T Cell Dysfunction in Chronic HCV Infection","abstract":"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.","abstract_html":"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.","abstract_has_math":false,"creators":["Ahmed, Faria"],"institution":"Université d'Ottawa / University of Ottawa","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Kumar, Ashok"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018-10-02T18:17:44Z","date_published":"2018-10-02T18:17:44Z","updated_at":"2026-07-24T03:39:29Z","subjects":["HCV","Hepatitis C","Chronic Infection","Immunology","Innate","Adaptive","Macrophages","T cells","Immune Response"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["http://dx.doi.org/10.20381/ruor-22481"],"render_values":[{"text":"http://dx.doi.org/10.20381/ruor-22481","href":"http://dx.doi.org/10.20381/ruor-22481","code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/10393/38227","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Kumar, Ashok"]},{"key":"dc:creator","label":"Author","values":["Ahmed, Faria"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2018-10-02T18:17:44Z","2019-10-02T09:00:09Z","2018-10-02"]},{"key":"dc:publisher","label":"Institution","values":["Université d'Ottawa / University of Ottawa"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["HCV","Hepatitis C","Chronic Infection","Immunology","Innate","Adaptive","Macrophages","T cells","Immune Response"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10393/38227","http://dx.doi.org/10.20381/ruor-22481"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["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."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Role of Macrophage Subsets in CD8+ T Cell Dysfunction in Chronic HCV Infection"]}]}],"canonical_facts":{"dc:contributor":["Kumar, Ashok"],"dc:creator":["Ahmed, Faria"],"dc:date":["2018-10-02T18:17:44Z","2019-10-02T09:00:09Z","2018-10-02"],"dc:description":["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."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10393/38227","http://dx.doi.org/10.20381/ruor-22481"],"dc:language":["en"],"dc:publisher":["Université d'Ottawa / University of Ottawa"],"dc:subject":["HCV","Hepatitis C","Chronic Infection","Immunology","Innate","Adaptive","Macrophages","T cells","Immune Response"],"dc:title":["Role of Macrophage Subsets in CD8+ T Cell Dysfunction in Chronic HCV Infection"],"dc:type":["Thesis"]},"updated_at":"2026-07-24T03:39:29Z"}