The immunobiology and the control of experimental visceral leishmaniasis were studied in susceptible (C57BL/6J) and resistant (C57L/J) strains of mice. It was found that the resistant/susceptibility phenotype for infection with L. donovani is expressed only by liver macrophage in vitro; the resistant/susceptible phenotypes were transfered reciprocally by bone marrow radiation chimeras. It was also found that the phagocytic activity of macrophages is reduced by the infection and that liver and peritoneal macrophages reflect their specific resistance/susceptibility phenotype following protective or curative treatment with lymphokines: macrophages from resistant C57L/J mice responded better to lymphokine activation. The production of IL-1 by spleen and peritoneal macrophages is inhibited by the infection. Immunosuppression with cyclosporin A (CsA) exacerbated the infection, without affecting phenotype; both CsA-treated strains of mice heal the infection in the absence of IL-1 and IL-2. There were more infected liver macrophages in normal or CsA-treated susceptible C57BL/6J mice and a greater number of amastigotes per cell than in normal or CsA-treated resistant C57L/J mice. CsA treatment did not affect the responsiveness of macrophages to lymphokine activation. IL-2-treated spleen and blood leucocytes from infected animals reduced infection in macrophages infected in vitro. Adoptive immunotherapy in vivo with IL-2-treated spleen cells from infected animals showed significant specific reduction of the parasite load in the liver; daily injections of IL-2 enhanced cure. T lymphocytes are the cells involved in cure; cure is mediated by soluble factors produced by the treated cells, and is specific to Leishmania infection.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.74363 |
| Date | January 1988 |
| Creators | Olivier, Martin |
| 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 (Institute of Parasitology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001071099, proquestno: AAINN64103, Theses scanned by UMI/ProQuest. |
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