Thymic Development of Microbe-Specific T Cells and Their Effects on Antimicrobial Antibody Responses
| dc.contributor.advisor | Geuking, Markus | |
| dc.contributor.author | Wilson, Kirsten | |
| dc.contributor.committeemember | Peters, Nathan | |
| dc.contributor.committeemember | McDonald, Braedon | |
| dc.date | Spring Convocation | |
| dc.date.accessioned | 2023-04-04T18:15:28Z | |
| dc.date.embargolift | 2023-04-13 | |
| dc.date.issued | 2022-03-24 | |
| dc.description.abstract | The body of literature surrounding interactions between the microbiota, T cells and B cells has grown substantially in recent years, but several questions remain. This thesis worked towards filling knowledge gaps in this field. Research from the Geuking lab has shown that mice primed with E. coli_gp61 produced a significantly greater E. coli-specific immunoglobulin (Ig) response compared to mice challenged with wild-type (WT) E. coli. My research has shown these antimicrobial antibodies to be T cell dependent with Class Switch Recombination (CSR) increasing bacterial specific IgM on day 7 and bacterial specific IgG on day 14. Following this finding, it was determined that in vitro fitness of E. coli is comparable between WT E. coli, E. coli_gp61 and E. coli_OmpC KO, but these bacteria display unique metabolic profiles with E. coli_gp61 and E. coli_OmpC KO displaying the most similarities. To test the effect of bacterial antigens in the thymus as well as the effect of metabolites on selection in the thymus, an organotypic thymic culture system was then utilized. Thymic slices were able to recognize pure peptide but were unable to independently process and present bacterial antigens. Intestinal-derived bacterial metabolites were able to reach the thymus and modulate negative selection and nTreg generation shown by GF mice producing more nTregs and having less CD4+CD8+ cells in response to self-peptide compared to sDMDMm2 or SPF mice. Finally, Recent Thymic Emigrants (RTEs) showed comparable thymic output in vivo between GF and SPF mice. Overall, these results show important differences between both thymic development of microbe-specific T cells and their effects on systemic antimicrobial antibody responses in GF and SPF mice, adding to our body of knowledge surrounding microbiota, T cell and B cell interactions. | |
| dc.identifier.citation | Wilson, K. (2022). Thymic Development of Microbe-Specific T Cells and Their Effects on Antimicrobial Antibody Responses (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. | |
| dc.identifier.uri | https://prism.ucalgary.ca/handle/1880/116034 | |
| dc.identifier.uri | https://dx.doi.org/10.11575/PRISM/dspace/40880 | |
| dc.language.iso | English | |
| dc.publisher.faculty | Cumming School of Medicine | |
| dc.subject | T cells | |
| dc.subject | Microbiota | |
| dc.subject.classification | Biology--Cell | |
| dc.title | Thymic Development of Microbe-Specific T Cells and Their Effects on Antimicrobial Antibody Responses | |
| dc.type | master thesis | |
| thesis.degree.discipline | Medicine – Immunology | |
| thesis.degree.grantor | University of Calgary | |
| thesis.degree.name | Master of Science (MSc) |