{"id":{"repo_id":"utmb","oai_identifier":"oai:utmb-ir.tdl.org:2152.3/712"},"canonical_url":"https://search.dev.ndltd.org/etd/utmb/oai:utmb-ir.tdl.org:2152.3/712","repository":{"repo_id":"utmb","name":"University of Texas Medical Branch","base_url":"https://utmb-ir.tdl.org/server/oai/request"},"display":{"title":"Helicobacter pylori Type 4 Secretion System Modulates Host T Cell Responses","abstract":"Infection with Helicobacter pylori (H. pylori) bacteria is associated with gastritis, peptic ulcer, and gastric cancer. During H. pylori infection CD4+ T cells in the gastric lamina propria are hyporesponsive and polarized to Th1/Th17 cell responses controlled by Treg cells. Gastric epithelial cells (GECs) are the primary target for H. pylori infection and may act as antigen-presenting cells (APCs) regulating local T cell responses. Previously our lab showed that H. pylori up-regulates B7-H1 (a T cell co-inhibitory molecule) expression on GEC, which, in turn, suppress T cell proliferation and effector function, and induce Treg cells in vitro. My studies showed that, along with B7-H1, GEC expresses B7-H2 and B7-H3 molecules. B7-H2 is a T cell co-stimulatory molecule, and B7-H3 has both co-stimulatory and inhibitory functions. Moreover, their expression is modulated during H. pylori infection. In addition, I investigated the underlying mechanisms of these responses-and demonstrated that H. pylori requires its type 4 secretion system (T4SS) translocated components: effector protein CagA and cell-wall peptidoglycan (PG) fragments for up-regulating B7-H1 as well as B7-H3, and for down-regulating B7-H2 on GEC. These data were validated in vivo by using a mouse model of infection. My study demonstrated that, along with T4SS, cytokines produced by Th17 and Treg cells also induce B7-H3 expression. I evaluated the underlying cell signaling pathways and showed that H. pylori uses the p38 MAPK pathway to up-regulate B7-H1 and B7-H3 expression and the p70S6/mTOR pathway for B7-H2 down-regulation in GEC. By using in vitro and in vivo systems, I demonstrated that H. pylori T4SS-mediated up-regulation of B7-H1 expression by GEC caused Treg cell induction and increased bacterial loads whereas H. pylori CagA-mediated B7-H2 down-regulation in GECs correlated with a decrease in Th17-type responses. Furthermore, the modulation of Th17 responses inversely correlated with the H. pylori colonization levels. Finally, the up-regulation of B7-H3 expression resulted in induction of Th2 cells in vitro and in vivo. In conclusion, these studies revealed some novel regulatory mechanisms employed by H. pylori to influence the type of T cell response that develops in the infected gastric mucosa and help in establishing chronic infection there.","abstract_html":"Infection with Helicobacter pylori (H. pylori) bacteria is associated with gastritis, peptic ulcer, and gastric cancer. During H. pylori infection CD4+ T cells in the gastric lamina propria are hyporesponsive and polarized to Th1/Th17 cell responses controlled by Treg cells. Gastric epithelial cells (GECs) are the primary target for H. pylori infection and may act as antigen-presenting cells (APCs) regulating local T cell responses. Previously our lab showed that H. pylori up-regulates B7-H1 (a T cell co-inhibitory molecule) expression on GEC, which, in turn, suppress T cell proliferation and effector function, and induce Treg cells in vitro. My studies showed that, along with B7-H1, GEC expresses B7-H2 and B7-H3 molecules. B7-H2 is a T cell co-stimulatory molecule, and B7-H3 has both co-stimulatory and inhibitory functions. Moreover, their expression is modulated during H. pylori infection. In addition, I investigated the underlying mechanisms of these responses-and demonstrated that H. pylori requires its type 4 secretion system (T4SS) translocated components: effector protein CagA and cell-wall peptidoglycan (PG) fragments for up-regulating B7-H1 as well as B7-H3, and for down-regulating B7-H2 on GEC. These data were validated in vivo by using a mouse model of infection. My study demonstrated that, along with T4SS, cytokines produced by Th17 and Treg cells also induce B7-H3 expression. I evaluated the underlying cell signaling pathways and showed that H. pylori uses the p38 MAPK pathway to up-regulate B7-H1 and B7-H3 expression and the p70S6/mTOR pathway for B7-H2 down-regulation in GEC. By using in vitro and in vivo systems, I demonstrated that H. pylori T4SS-mediated up-regulation of B7-H1 expression by GEC caused Treg cell induction and increased bacterial loads whereas H. pylori CagA-mediated B7-H2 down-regulation in GECs correlated with a decrease in Th17-type responses. Furthermore, the modulation of Th17 responses inversely correlated with the H. pylori colonization levels. Finally, the up-regulation of B7-H3 expression resulted in induction of Th2 cells in vitro and in vivo. In conclusion, these studies revealed some novel regulatory mechanisms employed by H. pylori to influence the type of T cell response that develops in the infected gastric mucosa and help in establishing chronic infection there.","abstract_has_math":false,"creators":["Lina, Taslima Taher"],"institution":"The University of Texas Medical Branch at Galveston","degree_name":"Microbiology and Immunology (Doctoral)","degree_level":"Doctoral","degree_discipline":"Immunology","degree_department":null,"school":null,"contributors":[],"advisors":["Reyes, Victor E"],"committee_chairs":[],"committee_members":["Torres, Alfredo G.","Pinchuk, Iryna V.","Bao , Xiaoyong","Beswick, Ellen J."],"year":null,"date_issued":"","date_published":null,"updated_at":"2026-07-24T05:51:04Z","subjects":["Helicobacter pylori, Type 4 secretion system, CagA, B7-H1, B7-H2, B7-H3, Gastric epithelial cells, Treg cells, Th17 cells"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2152.3/712","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Reyes, Victor E"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Torres, Alfredo G.","Pinchuk, Iryna V.","Bao , Xiaoyong","Beswick, Ellen J."]},{"key":"dc:creator","label":"Author","values":["Lina, Taslima Taher"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2016-05-05T21:53:40Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2016-05-05T21:53:40Z"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Immunology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Microbiology and Immunology (Doctoral)"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The University of Texas Medical Branch at Galveston"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Helicobacter pylori, Type 4 secretion system, CagA, B7-H1, B7-H2, B7-H3, Gastric epithelial cells, Treg cells, Th17 cells"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/2152.3/712"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Infection with Helicobacter pylori (H. pylori) bacteria is associated with gastritis, peptic ulcer, and gastric cancer. During H. pylori infection CD4+ T cells in the gastric lamina propria are hyporesponsive and polarized to Th1/Th17 cell responses controlled by Treg cells. Gastric epithelial cells (GECs) are the primary target for H. pylori infection and may act as antigen-presenting cells (APCs) regulating local T cell responses. Previously our lab showed that H. pylori up-regulates B7-H1 (a T cell co-inhibitory molecule) expression on GEC, which, in turn, suppress T cell proliferation and effector function, and induce Treg cells in vitro. My studies showed that, along with B7-H1, GEC expresses B7-H2 and B7-H3 molecules. B7-H2 is a T cell co-stimulatory molecule, and B7-H3 has both co-stimulatory and inhibitory functions. Moreover, their expression is modulated during H. pylori infection. In addition, I investigated the underlying mechanisms of these responses-and demonstrated that H. pylori requires its type 4 secretion system (T4SS) translocated components: effector protein CagA and cell-wall peptidoglycan (PG) fragments for up-regulating B7-H1 as well as B7-H3, and for down-regulating B7-H2 on GEC. These data were validated in vivo by using a mouse model of infection. My study demonstrated that, along with T4SS, cytokines produced by Th17 and Treg cells also induce B7-H3 expression. I evaluated the underlying cell signaling pathways and showed that H. pylori uses the p38 MAPK pathway to up-regulate B7-H1 and B7-H3 expression and the p70S6/mTOR pathway for B7-H2 down-regulation in GEC. By using in vitro and in vivo systems, I demonstrated that H. pylori T4SS-mediated up-regulation of B7-H1 expression by GEC caused Treg cell induction and increased bacterial loads whereas H. pylori CagA-mediated B7-H2 down-regulation in GECs correlated with a decrease in Th17-type responses. Furthermore, the modulation of Th17 responses inversely correlated with the H. pylori colonization levels. Finally, the up-regulation of B7-H3 expression resulted in induction of Th2 cells in vitro and in vivo. In conclusion, these studies revealed some novel regulatory mechanisms employed by H. pylori to influence the type of T cell response that develops in the infected gastric mucosa and help in establishing chronic infection there."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Helicobacter pylori Type 4 Secretion System Modulates Host T Cell Responses"]}]}],"canonical_facts":{"dc:contributor.advisor":["Reyes, Victor E"],"dc:contributor.committeemember":["Torres, Alfredo G.","Pinchuk, Iryna V.","Bao , Xiaoyong","Beswick, Ellen J."],"dc:creator":["Lina, Taslima Taher"],"dc:date.accessioned":["2016-05-05T21:53:40Z"],"dc:date.available":["2016-05-05T21:53:40Z"],"dc:description.abstract":["Infection with Helicobacter pylori (H. pylori) bacteria is associated with gastritis, peptic ulcer, and gastric cancer. During H. pylori infection CD4+ T cells in the gastric lamina propria are hyporesponsive and polarized to Th1/Th17 cell responses controlled by Treg cells. Gastric epithelial cells (GECs) are the primary target for H. pylori infection and may act as antigen-presenting cells (APCs) regulating local T cell responses. Previously our lab showed that H. pylori up-regulates B7-H1 (a T cell co-inhibitory molecule) expression on GEC, which, in turn, suppress T cell proliferation and effector function, and induce Treg cells in vitro. My studies showed that, along with B7-H1, GEC expresses B7-H2 and B7-H3 molecules. B7-H2 is a T cell co-stimulatory molecule, and B7-H3 has both co-stimulatory and inhibitory functions. Moreover, their expression is modulated during H. pylori infection. In addition, I investigated the underlying mechanisms of these responses-and demonstrated that H. pylori requires its type 4 secretion system (T4SS) translocated components: effector protein CagA and cell-wall peptidoglycan (PG) fragments for up-regulating B7-H1 as well as B7-H3, and for down-regulating B7-H2 on GEC. These data were validated in vivo by using a mouse model of infection. My study demonstrated that, along with T4SS, cytokines produced by Th17 and Treg cells also induce B7-H3 expression. I evaluated the underlying cell signaling pathways and showed that H. pylori uses the p38 MAPK pathway to up-regulate B7-H1 and B7-H3 expression and the p70S6/mTOR pathway for B7-H2 down-regulation in GEC. By using in vitro and in vivo systems, I demonstrated that H. pylori T4SS-mediated up-regulation of B7-H1 expression by GEC caused Treg cell induction and increased bacterial loads whereas H. pylori CagA-mediated B7-H2 down-regulation in GECs correlated with a decrease in Th17-type responses. Furthermore, the modulation of Th17 responses inversely correlated with the H. pylori colonization levels. Finally, the up-regulation of B7-H3 expression resulted in induction of Th2 cells in vitro and in vivo. In conclusion, these studies revealed some novel regulatory mechanisms employed by H. pylori to influence the type of T cell response that develops in the infected gastric mucosa and help in establishing chronic infection there."],"dc:format.mimetype":["application/pdf"],"dc:identifier.uri":["http://hdl.handle.net/2152.3/712"],"dc:subject":["Helicobacter pylori, Type 4 secretion system, CagA, B7-H1, B7-H2, B7-H3, Gastric epithelial cells, Treg cells, Th17 cells"],"dc:title":["Helicobacter pylori Type 4 Secretion System Modulates Host T Cell Responses"],"dc:type":["Thesis"],"thesis:degree_discipline":["Immunology"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Microbiology and Immunology (Doctoral)"],"thesis:institution_name":["The University of Texas Medical Branch at Galveston"]},"updated_at":"2026-07-24T05:51:04Z"}