{"id":{"repo_id":"sask","oai_identifier":"oai:harvest.usask.ca:10388/ETD-2015-06-2123"},"canonical_url":"https://search.dev.ndltd.org/etd/sask/oai:harvest.usask.ca:10388/ETD-2015-06-2123","repository":{"repo_id":"sask","name":"University of Saskatchewan","base_url":"https://harvest.usask.ca/server/oai/request"},"display":{"title":"The interactions of tolerogenic dendritic cells, induced regulatory T cells and antigen-specific IgG1-secreting plasma cells in asthma","abstract":"Allergic asthma is a chronic inflammatory airway disease that is dominated by Th2 immune responses, with accumulation of eosinophils, IgE and IgG1 production, and airway hyperresponsiveness. We reported previously that treatment of OVA-asthmatic mice with allergen-presenting IL-10-differentiated dendritic cells (DC) (DC10) leads to progressive and long-lasting full-spectrum asthma tolerance. However, little has been done in investigating a role for antigen-specific B cells in DC10-induced tolerance. In this study, we characterized the surface markers of DC10 and found that these cells expressed lower levels of CD40, CD80, MHC II, PD-L1 and PD-L2 relative to immunostimulatory LPS-differentiated DCs (DCLPS). Co-culturing DC10 or DC10-induced regulatory T cells (iTreg) with CD4+ Th2 effector T cells from asthmatic mice led to a marked suppression of DCLPS-induced T effector cell proliferation. Moreover, DC10 treatment of asthma phenotype mice down-regulated airway eosinophilic inflammation as determined 48 h after a recall allergen challenge, and reduced pulmonary parenchymal tissue OVA-specific IgG1-secreting (OVA-IgG1) plasma cell numbers. The number of lung OVA-specific IgG1 plasma cells decreased by 46.7% over a 2 week period in the absence of repeated allergen challenge, while the numbers of bone marrow OVA-specific IgG1 plasma cells stayed relatively stable over a 6 week period, as determined 48 h after a single allergen challenge of asthmatic mice. DC10 treatment had a significant impact on the serum of IgG1/IgE response. To address the question of how DC10 influence OVA-IgG1 plasma cells responses, we co-cultured enzymatically-dispersed lung total cells from asthmatic mice with or without DC10, and found that the DC10 significantly suppressed OVA-IgG1 plasma cell antibody production. To determine whether DC10 required input from T cells to accomplish this, we co-cultured CD4 T cell-depleted, B cell-enriched populations from the lungs of asthmatic mice with or without DC10, and found that DC10 strongly (65.4+/-3.5%) suppressed OVA-IgG1 plasma cells in CD4 T cell-depleted lung cell cultures. To assess whether DC10-induced Treg also suppress IgG1-secretion, we co-cultured lung CD4+ T cells from untreated or DC10-tolerized asthmatic mice with total lung cells from asthmatic donors, and found that the DC10-induced Tregs effectively (52.2+/-8.7%) suppressed OVA-IgG1 plasma cell responses. In summary, DC10 treatment strongly down-regulate OVA-specific IgG1 plasma cell responses of asthmatic mice, both in vivo and in vitro by at least two mechanisms: directly via DC10 as well as indirectly through DC10-induced Tregs.","abstract_html":"Allergic asthma is a chronic inflammatory airway disease that is dominated by Th2 immune responses, with accumulation of eosinophils, IgE and IgG1 production, and airway hyperresponsiveness. We reported previously that treatment of OVA-asthmatic mice with allergen-presenting IL-10-differentiated dendritic cells (DC) (DC10) leads to progressive and long-lasting full-spectrum asthma tolerance. However, little has been done in investigating a role for antigen-specific B cells in DC10-induced tolerance. In this study, we characterized the surface markers of DC10 and found that these cells expressed lower levels of CD40, CD80, MHC II, PD-L1 and PD-L2 relative to immunostimulatory LPS-differentiated DCs (DCLPS). Co-culturing DC10 or DC10-induced regulatory T cells (iTreg) with CD4+ Th2 effector T cells from asthmatic mice led to a marked suppression of DCLPS-induced T effector cell proliferation. Moreover, DC10 treatment of asthma phenotype mice down-regulated airway eosinophilic inflammation as determined 48 h after a recall allergen challenge, and reduced pulmonary parenchymal tissue OVA-specific IgG1-secreting (OVA-IgG1) plasma cell numbers. The number of lung OVA-specific IgG1 plasma cells decreased by 46.7% over a 2 week period in the absence of repeated allergen challenge, while the numbers of bone marrow OVA-specific IgG1 plasma cells stayed relatively stable over a 6 week period, as determined 48 h after a single allergen challenge of asthmatic mice. DC10 treatment had a significant impact on the serum of IgG1/IgE response. To address the question of how DC10 influence OVA-IgG1 plasma cells responses, we co-cultured enzymatically-dispersed lung total cells from asthmatic mice with or without DC10, and found that the DC10 significantly suppressed OVA-IgG1 plasma cell antibody production. To determine whether DC10 required input from T cells to accomplish this, we co-cultured CD4 T cell-depleted, B cell-enriched populations from the lungs of asthmatic mice with or without DC10, and found that DC10 strongly (65.4+/-3.5%) suppressed OVA-IgG1 plasma cells in CD4 T cell-depleted lung cell cultures. To assess whether DC10-induced Treg also suppress IgG1-secretion, we co-cultured lung CD4+ T cells from untreated or DC10-tolerized asthmatic mice with total lung cells from asthmatic donors, and found that the DC10-induced Tregs effectively (52.2+/-8.7%) suppressed OVA-IgG1 plasma cell responses. In summary, DC10 treatment strongly down-regulate OVA-specific IgG1 plasma cell responses of asthmatic mice, both in vivo and in vitro by at least two mechanisms: directly via DC10 as well as indirectly through DC10-induced Tregs.","abstract_has_math":false,"creators":["Ma, Yanna"],"institution":"University of Saskatchewan","degree_name":"Master of Science (M.Sc.)","degree_level":"Masters","degree_discipline":"Health Sciences","degree_department":null,"school":null,"contributors":[],"advisors":["Gordon, John R."],"committee_chairs":[],"committee_members":["Gerdts, Volker","Ziola, Barry","Singh, Baljit","Cockcroft, Donald"],"year":2015,"date_issued":"2015-09-08","date_published":"2015-09-08","updated_at":"2026-07-24T04:26:57Z","subjects":["Tolerogenic dendritic cells","Induced regulatory T cells","Antigen-specific IgG1-secreting plasma cells","Asthma"],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/10388/ETD-2015-06-2123","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Gordon, John R."]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Gerdts, Volker","Ziola, Barry","Singh, Baljit","Cockcroft, Donald"]},{"key":"dc:creator","label":"Author","values":["Ma, Yanna"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2015-09-09T12:00:14Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2015-09-09T12:00:14Z"]},{"key":"dc:date.issued","label":"Date","values":["2015-09-08"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Health Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Masters"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science (M.Sc.)"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Saskatchewan"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Tolerogenic dendritic cells","Induced regulatory T cells","Antigen-specific IgG1-secreting plasma cells","Asthma"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/10388/ETD-2015-06-2123"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Allergic asthma is a chronic inflammatory airway disease that is dominated by Th2 immune responses, with accumulation of eosinophils, IgE and IgG1 production, and airway hyperresponsiveness. We reported previously that treatment of OVA-asthmatic mice with allergen-presenting IL-10-differentiated dendritic cells (DC) (DC10) leads to progressive and long-lasting full-spectrum asthma tolerance. However, little has been done in investigating a role for antigen-specific B cells in DC10-induced tolerance. In this study, we characterized the surface markers of DC10 and found that these cells expressed lower levels of CD40, CD80, MHC II, PD-L1 and PD-L2 relative to immunostimulatory LPS-differentiated DCs (DCLPS). Co-culturing DC10 or DC10-induced regulatory T cells (iTreg) with CD4+ Th2 effector T cells from asthmatic mice led to a marked suppression of DCLPS-induced T effector cell proliferation. Moreover, DC10 treatment of asthma phenotype mice down-regulated airway eosinophilic inflammation as determined 48 h after a recall allergen challenge, and reduced pulmonary parenchymal tissue OVA-specific IgG1-secreting (OVA-IgG1) plasma cell numbers. The number of lung OVA-specific IgG1 plasma cells decreased by 46.7% over a 2 week period in the absence of repeated allergen challenge, while the numbers of bone marrow OVA-specific IgG1 plasma cells stayed relatively stable over a 6 week period, as determined 48 h after a single allergen challenge of asthmatic mice. DC10 treatment had a significant impact on the serum of IgG1/IgE response. To address the question of how DC10 influence OVA-IgG1 plasma cells responses, we co-cultured enzymatically-dispersed lung total cells from asthmatic mice with or without DC10, and found that the DC10 significantly suppressed OVA-IgG1 plasma cell antibody production. To determine whether DC10 required input from T cells to accomplish this, we co-cultured CD4 T cell-depleted, B cell-enriched populations from the lungs of asthmatic mice with or without DC10, and found that DC10 strongly (65.4+/-3.5%) suppressed OVA-IgG1 plasma cells in CD4 T cell-depleted lung cell cultures. To assess whether DC10-induced Treg also suppress IgG1-secretion, we co-cultured lung CD4+ T cells from untreated or DC10-tolerized asthmatic mice with total lung cells from asthmatic donors, and found that the DC10-induced Tregs effectively (52.2+/-8.7%) suppressed OVA-IgG1 plasma cell responses. In summary, DC10 treatment strongly down-regulate OVA-specific IgG1 plasma cell responses of asthmatic mice, both in vivo and in vitro by at least two mechanisms: directly via DC10 as well as indirectly through DC10-induced Tregs."]},{"key":"dc:title","label":"Title","values":["The interactions of tolerogenic dendritic cells, induced regulatory T cells and antigen-specific IgG1-secreting plasma cells in asthma"]}]}],"canonical_facts":{"dc:contributor.advisor":["Gordon, John R."],"dc:contributor.committeemember":["Gerdts, Volker","Ziola, Barry","Singh, Baljit","Cockcroft, Donald"],"dc:creator":["Ma, Yanna"],"dc:date.accessioned":["2015-09-09T12:00:14Z"],"dc:date.available":["2015-09-09T12:00:14Z"],"dc:date.issued":["2015-09-08"],"dc:description.abstract":["Allergic asthma is a chronic inflammatory airway disease that is dominated by Th2 immune responses, with accumulation of eosinophils, IgE and IgG1 production, and airway hyperresponsiveness. We reported previously that treatment of OVA-asthmatic mice with allergen-presenting IL-10-differentiated dendritic cells (DC) (DC10) leads to progressive and long-lasting full-spectrum asthma tolerance. However, little has been done in investigating a role for antigen-specific B cells in DC10-induced tolerance. In this study, we characterized the surface markers of DC10 and found that these cells expressed lower levels of CD40, CD80, MHC II, PD-L1 and PD-L2 relative to immunostimulatory LPS-differentiated DCs (DCLPS). Co-culturing DC10 or DC10-induced regulatory T cells (iTreg) with CD4+ Th2 effector T cells from asthmatic mice led to a marked suppression of DCLPS-induced T effector cell proliferation. Moreover, DC10 treatment of asthma phenotype mice down-regulated airway eosinophilic inflammation as determined 48 h after a recall allergen challenge, and reduced pulmonary parenchymal tissue OVA-specific IgG1-secreting (OVA-IgG1) plasma cell numbers. The number of lung OVA-specific IgG1 plasma cells decreased by 46.7% over a 2 week period in the absence of repeated allergen challenge, while the numbers of bone marrow OVA-specific IgG1 plasma cells stayed relatively stable over a 6 week period, as determined 48 h after a single allergen challenge of asthmatic mice. DC10 treatment had a significant impact on the serum of IgG1/IgE response. To address the question of how DC10 influence OVA-IgG1 plasma cells responses, we co-cultured enzymatically-dispersed lung total cells from asthmatic mice with or without DC10, and found that the DC10 significantly suppressed OVA-IgG1 plasma cell antibody production. To determine whether DC10 required input from T cells to accomplish this, we co-cultured CD4 T cell-depleted, B cell-enriched populations from the lungs of asthmatic mice with or without DC10, and found that DC10 strongly (65.4+/-3.5%) suppressed OVA-IgG1 plasma cells in CD4 T cell-depleted lung cell cultures. To assess whether DC10-induced Treg also suppress IgG1-secretion, we co-cultured lung CD4+ T cells from untreated or DC10-tolerized asthmatic mice with total lung cells from asthmatic donors, and found that the DC10-induced Tregs effectively (52.2+/-8.7%) suppressed OVA-IgG1 plasma cell responses. In summary, DC10 treatment strongly down-regulate OVA-specific IgG1 plasma cell responses of asthmatic mice, both in vivo and in vitro by at least two mechanisms: directly via DC10 as well as indirectly through DC10-induced Tregs."],"dc:identifier.uri":["https://hdl.handle.net/10388/ETD-2015-06-2123"],"dc:language.iso":["eng"],"dc:subject":["Tolerogenic dendritic cells","Induced regulatory T cells","Antigen-specific IgG1-secreting plasma cells","Asthma"],"dc:title":["The interactions of tolerogenic dendritic cells, induced regulatory T cells and antigen-specific IgG1-secreting plasma cells in asthma"],"thesis:degree_discipline":["Health Sciences"],"thesis:degree_level":["Masters"],"thesis:degree_name":["Master of Science (M.Sc.)"],"thesis:institution_name":["University of Saskatchewan"]},"updated_at":"2026-07-24T04:26:57Z"}