{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/80970"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/80970","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Essential Role of CD27/CD70 Pathway in Inflammatory T Cell Response","abstract":"Ph.D.","abstract_html":"Ph.D.","abstract_has_math":false,"creators":["O'Neill, Rachel"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Cao, Xuefang","Roswell Park"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-10-29T16:48:36Z","date_published":"2019-10-29T16:48:36Z","updated_at":"2026-07-27T19:05:28Z","subjects":["immunology"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/80970","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Cao, Xuefang","Roswell Park"]},{"key":"dc:creator","label":"Author","values":["O'Neill, Rachel"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-10-29T16:48:36Z","2019","2019-08-28 12:39:52"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation","Text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["immunology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/80970"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Ph.D.","Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for a variety of hematologic and immunologic diseases. However, graft-versus-host disease (GVHD) remains the major complication that causes significant morbidity and mortality despite the currently practiced immunosuppressive therapies. New approaches for controlling GVHD while preserving the beneficial graft-versus-leukemia/lymphoma (GVL) effect are necessary if we hope to achieve the curative potential of allo-HCT, which requires a better understanding of the underlying mechanisms. GVHD is known to be caused by donor-derived T cells that recognize allogeneic antigens expressed on host cells and subsequently damage host normal tissue. In addition to TCR signaling stimulated by MHC-antigen complex, co-stimulatory pathways are involved in T cell activation and function. The co-stimulatory molecule CD27 is a TNF receptor family member constitutively expressed on T cells, B cells and NK cells and its ligand, CD70, is known to be expressed on activated antigen-presenting cells (APC) as well as T cells. Interaction of CD27 and CD70 in inflammatory conditions has been shown to cause immune dysregulation and immunopathology. However, the role of this pathway in an allogeneic transplantation setting is previously unknown. The CD27-CD70 pathway is known to provide a costimulatory signal with CD70 expressed on antigen-presenting cells while CD27 functioning on T cells. Although CD70 is also expressed on activated T cells, it remains unclear how T cell-derived CD70 affects T cell function. Therefore, we have assessed the role of T cell intrinsic CD70 using adoptive transfer models including autoimmune inflammatory bowel disease (IBD) and allogeneic graft-versus-host disease (GVHD). Compared with WT T cells, CD70-/- T cells xi surprisingly caused more severe IBD and GVHD and produced higher levels of inflammatory cytokines. Mechanistic analyses reveal that IFN- induces CD70 expression in T cells, and CD70 limits T cell expansion via a regulatory T cell-independent mechanism that involves caspase-dependent T cell apoptosis and up-regulation of inhibitory immune checkpoint molecules. Overall, our findings demonstrate for the first time that T cell-derived CD70 plays a novel immune checkpoint role in inhibiting inflammatory T cell responses. This study suggests that T cell-derived CD70 performs a critical negative feedback function to down-regulate inflammatory T cell responses. Following lethal irradiation, emergency hematopoiesis of stem cells occurs in the bone marrow niches."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Essential Role of CD27/CD70 Pathway in Inflammatory T Cell Response"]}]}],"canonical_facts":{"dc:contributor":["Cao, Xuefang","Roswell Park"],"dc:creator":["O'Neill, Rachel"],"dc:date":["2019-10-29T16:48:36Z","2019","2019-08-28 12:39:52"],"dc:description":["Ph.D.","Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for a variety of hematologic and immunologic diseases. However, graft-versus-host disease (GVHD) remains the major complication that causes significant morbidity and mortality despite the currently practiced immunosuppressive therapies. New approaches for controlling GVHD while preserving the beneficial graft-versus-leukemia/lymphoma (GVL) effect are necessary if we hope to achieve the curative potential of allo-HCT, which requires a better understanding of the underlying mechanisms. GVHD is known to be caused by donor-derived T cells that recognize allogeneic antigens expressed on host cells and subsequently damage host normal tissue. In addition to TCR signaling stimulated by MHC-antigen complex, co-stimulatory pathways are involved in T cell activation and function. The co-stimulatory molecule CD27 is a TNF receptor family member constitutively expressed on T cells, B cells and NK cells and its ligand, CD70, is known to be expressed on activated antigen-presenting cells (APC) as well as T cells. Interaction of CD27 and CD70 in inflammatory conditions has been shown to cause immune dysregulation and immunopathology. However, the role of this pathway in an allogeneic transplantation setting is previously unknown. The CD27-CD70 pathway is known to provide a costimulatory signal with CD70 expressed on antigen-presenting cells while CD27 functioning on T cells. Although CD70 is also expressed on activated T cells, it remains unclear how T cell-derived CD70 affects T cell function. Therefore, we have assessed the role of T cell intrinsic CD70 using adoptive transfer models including autoimmune inflammatory bowel disease (IBD) and allogeneic graft-versus-host disease (GVHD). Compared with WT T cells, CD70-/- T cells xi surprisingly caused more severe IBD and GVHD and produced higher levels of inflammatory cytokines. Mechanistic analyses reveal that IFN- induces CD70 expression in T cells, and CD70 limits T cell expansion via a regulatory T cell-independent mechanism that involves caspase-dependent T cell apoptosis and up-regulation of inhibitory immune checkpoint molecules. Overall, our findings demonstrate for the first time that T cell-derived CD70 plays a novel immune checkpoint role in inhibiting inflammatory T cell responses. This study suggests that T cell-derived CD70 performs a critical negative feedback function to down-regulate inflammatory T cell responses. Following lethal irradiation, emergency hematopoiesis of stem cells occurs in the bone marrow niches."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/80970"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["immunology"],"dc:title":["Essential Role of CD27/CD70 Pathway in Inflammatory T Cell Response"],"dc:type":["Dissertation","Text"]},"updated_at":"2026-07-27T19:05:28Z"}