Under some circumstances CsA induces autoimmune phenomena. A lethal form of graft-versus-host disease occurs in irradiated recipients of syngeneic or autologous BM treated with CsA, following withdrawal of the drug. We could induce this disease in all rat strains tested (Lewis, ACI, BN), but in only one mouse strain, i.e. DBA/2. The AKR, C57BR, CBA/J, C57B1/6 and SJL mouse strains were resistant to disease induction. We studied the effects of CsA on T cell maturation and clonal deletion in rats and mice. We found (as have others) that in the thymus CsA partially blocks the generation of mature-type T cells. In the periphery, we observed the transient appearance of an unusual population of CD4+CD8+ T cells. The T cells of CsA-treated mice of several strains, including diseased DBA/2 mice, showed a normal pattern of clonal deletion when analyzed for expression of TcR Vbeta6 and Vbeta17. Disease could be prevented in rats and mice by injecting normal spleen cells. We postulate that CsA causes autoimmune disease by altering a population of suppressor cells, rather than by blocking clonal deletion.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.59427 |
| Date | January 1990 |
| Creators | Sanders, Richard |
| 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 | Master of Science (Department of Pathology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001233021, proquestno: AAIMM63616, Theses scanned by UMI/ProQuest. |
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