Graft versus host disease (GVHD) is a major complication of bone marrow transplantation and may also occur naturally through the transplacental passage of maternal lymphocytes to the fetus. GVHD is associated with a broad spectrum of immunological disorders as well as distinct pathological changes. Yet, the exact nature of the effector cells involved remains to be elucidated. Studies on natural killer cell activity in bone marrow transplant patients have led to the speculation that natural killer cells may be major effectors of GVHD-induced immunopathogenesis. / To determine the role played by natural killer cells in GVHD, a murine model of neonatal GVHD was established. Natural killer cell function was evaluated in lymphoid target organs at various times post induction and was found to be significantly augmented by seven days post-injection. The phenotype of the effector cell was determined by antibody depletion studies to be asialo GM1 positive, partially Thy-1 positive and glass wool non-adherent. Immunostaining indicated an increased frequency of asialo GM-1 positive cells in the spleens of GVHD-induced mice. These effectors were further determined to be predominantly of donor origin. / The in vivo role of these asialo GM-1 positive cells in the actual pathogenesis of GVHD was also investigated. Asialo GM1 positive cells were depleted from either the donor inoculum prior to injection or from the recipient in vivo post-injection. Only the depletion of asialo GM1 positive cells from the host in vivo was effective in reducing GVHD-associated morbidity. / The possible role of placental suppressive factors in the protection of the fetus was also examined using this model. Extracts derived from placental tissue were found to be sufficiently potent to suppress in vivo the development of acute GVHD. / Our findings indicate that donor-derived asialo GM-1 positive killer cells play a major role in the development of acute GVHD. In addition, factors associated with the placenta may provide a sufficient functional barrier to prevent the development of GVHD in the fetus as the result of the transplacental passage of maternal lymphocytes.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.75916 |
| Date | January 1988 |
| Creators | McGuinness, Ursula M. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Microbiology and Immunology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 000911123, proquestno: AAINL52300, Theses scanned by UMI/ProQuest. |
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