The interactions of tolerogenic dendritic cells, induced regulatory T cells and antigen-specific IgG1-secreting plasma cells in asthma
| dc.contributor.advisor | Gordon, John R. | en_US |
| dc.contributor.committeeMember | Gerdts, Volker | en_US |
| dc.contributor.committeeMember | Ziola, Barry | en_US |
| dc.contributor.committeeMember | Singh, Baljit | en_US |
| dc.contributor.committeeMember | Cockcroft, Donald | en_US |
| dc.creator | Ma, Yanna | en_US |
| dc.date.accessioned | 2015-09-09T12:00:14Z | |
| dc.date.available | 2015-09-09T12:00:14Z | |
| dc.date.created | 2015-06 | en_US |
| dc.date.issued | 2015-09-08 | en_US |
| dc.date.submitted | June 2015 | en_US |
| 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. | en_US |
| dc.identifier.uri | http://hdl.handle.net/10388/ETD-2015-06-2123 | en_US |
| dc.language.iso | eng | en_US |
| dc.subject | Tolerogenic dendritic cells | en_US |
| dc.subject | Induced regulatory T cells | en_US |
| dc.subject | Antigen-specific IgG1-secreting plasma cells | en_US |
| dc.subject | Asthma | en_US |
| dc.title | The interactions of tolerogenic dendritic cells, induced regulatory T cells and antigen-specific IgG1-secreting plasma cells in asthma | en_US |
| dc.type.genre | Thesis | en_US |
| dc.type.material | text | en_US |
| thesis.degree.department | Medicine | en_US |
| thesis.degree.discipline | Health Sciences | en_US |
| thesis.degree.grantor | University of Saskatchewan | en_US |
| thesis.degree.level | Masters | en_US |
| thesis.degree.name | Master of Science (M.Sc.) | en_US |