Role of Splenic B Cells and Gamma Delta T Cells in the Induction of Peripheral Tolerance Elicited Through the Anterior Chamber of the Eye
| dc.contributor.advisor | Niederkorn, Jerry Y. | en |
| dc.creator | Ashour, Hossam Mohamed | en |
| dc.date.accessioned | 2010-07-12T18:38:30Z | |
| dc.date.available | 2010-07-12T18:38:30Z | |
| dc.date.issued | 2006-12-19 | |
| dc.description.abstract | Anterior chamber-associated immune deviation (ACAID) is a form of peripheral tolerance that is induced by introducing antigens into the anterior chamber (AC) of the eye, and is maintained by antigen-specific regulatory T cells (Tregs). ACAID regulates harmful immune responses that can lead to irreparable injury to innocent bystander cells that are incapable of regeneration. ACAID is a product of complex cellular interactions that involve F4/80+ ocular antigen presenting cells (APC), NK T cells, B cells, gamma delta (gamma delta ) T cells, CD4+CD25+ Tregs, and CD8+ Tregs. Antigens injected into the AC are processed by F4/80+ antigen presenting cells (APC), which migrate to the thymus and spleen. In the spleen, ocular APC induce the development of antigen-specific B cells that act as ancillary APC and are required for ACAID induction. Results show that ocular APC elicit the generation and expansion of antigen-specific splenic B cells that induce ACAID. However, direct cell contact between ocular APC and splenic B cells is not necessary for the induction of ACAID B cells. Peripheral tolerance produced by ACAID requires the participation of ACAID B cells, which induce the generation of both CD4+ Tregs and CD8+ Tregs. Using in vitro and in vivo models of ACAID, we demonstrate that ACAID B cells must express both MHC class I and class II molecules for the generation of Tregs. This suggests that ACAID requires antigen presenting B cells that simultaneously present antigens on both MHC class I and class II molecules. Gamma delta T cells are also crucial for the generation of ACAID, but their function in ACAID is largely unknown. Several hypotheses were proposed for determining the functions of gamma delta T cells in ACAID. The results indicate that gamma delta T cells neither suppress DTH directly nor do they act as antigen presenting cells. However, gamma delta T cells were shown to secrete IL-10, thus facilitating the generation of ACAID Tregs. In addition, the contribution of gamma delta T cells in ACAID generation could be replaced by adding exogenous rmIL-10 to ACAID spleen cell cultures lacking gamma delta T cells. Throughout this dissertation, we have shed light on the roles of B cells and gamma delta T cells in ACAID and have found that B cells need to express both MHC I and MHC II in order to induce the generation of Tregs and that gamma delta T cells need to secrete IL-10 for ACAID to be generated. | en |
| dc.format.digitalOrigin | born digital | en |
| dc.format.medium | Electronic | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.oclc | 186506140 | |
| dc.identifier.uri | https://hdl.handle.net/2152.5/629 | |
| dc.language.iso | en | en |
| dc.subject | Peripheral Tolerance | en |
| dc.subject | Antigen Presentation | en |
| dc.subject | T-Lymphocytes, Regulatory | en |
| dc.title | Role of Splenic B Cells and Gamma Delta T Cells in the Induction of Peripheral Tolerance Elicited Through the Anterior Chamber of the Eye | en |
| dc.type | Thesis | en |
| dc.type.genre | dissertation | en |
| dc.type.material | Text | en |
| thesis.date.available | 2007-12-19 | |
| thesis.degree.department | Graduate School of Biomedical Sciences | en |
| thesis.degree.discipline | Immunology | en |
| thesis.degree.grantor | UT Southwestern Medical Center | en |
| thesis.degree.level | Doctoral | en |
| thesis.degree.name | Doctor of Philosophy | en |