| dc.contributor.author | Skaro, Anton Ivan. | en_US |
| dc.date.accessioned | 2014-10-21T12:38:46Z | |
| dc.date.available | 2003 | |
| dc.date.issued | 2003 | en_US |
| dc.identifier.other | AAINQ83708 | en_US |
| dc.identifier.uri | http://hdl.handle.net/10222/55933 | |
| dc.description | Allograft vasculopathy (AV) has emerged as the major obstacle to long-term survival in clinical heart transplantation. Immune events are implicated in the development of AV, but the cellular and molecular mechanisms involved remain unclear. | en_US |
| dc.description | In this thesis, we examined the role of T cell subsets (CD4+ and CD8+) and the effector mechanisms involved using knockout mice and adoptive cell transfer in a fully MHC-mismatched murine aortic allograft model of AV. | en_US |
| dc.description | The inhibition of CD8+ T cells or cytotoxic T lymphocyte (CTL) effector mechanisms led to preservation of medial smooth muscle cells and attenuation of AV. In contrast, CD4 deficient mice exhibited striking medial smooth muscle loss and intimal hyperplasia which was similar in extent to wildtype recipients. Moreover, CD8+ T cells are essential to the development of AV in the presence of cyclosporine A-based immunosuppression. | en_US |
| dc.description | The transfer of allo-primed CD8+ T lymphocytes into immunodeficient recombinase activating gene knockout (RAG-/-) mouse recipients of aortic allografts resulted in the development of AV, confirming that CD8+ effector T cells are sufficient to induce AV. In addition, we established that CD8+ T cell-mediated AV occurs by contact-dependent direct cytolysis and by a distinct interferon-gamma-dependent indirect effector pathway. Furthermore, AV mediated by CD8+ T cells, but not CD4+ T cells, is refractory to cyclosporine A treatment. Given the resistance of this cell type to conventional immunosuppression these results may have important therapeutic implications. The development of novel immunosuppressive agents capable of inhibiting CD8+ T cells might prevent AV in the clinic. | en_US |
| dc.description | Thesis (Ph.D.)--Dalhousie University (Canada), 2003. | en_US |
| dc.language | eng | en_US |
| dc.publisher | Dalhousie University | en_US |
| dc.publisher | | en_US |
| dc.subject | Health Sciences, Medicine and Surgery. | en_US |
| dc.subject | Health Sciences, Immunology. | en_US |
| dc.title | Role of effector CD8+ T cells in allograft vasculopathy. | en_US |
| dc.type | text | en_US |
| dc.contributor.degree | Ph.D. | en_US |
