Antigen-presentation to CD8+ T cells normally commences immediately after infection, which facilitates their rapid expansion and control of infection. Subsequently, these antigen-primed CD8+ T cells undergo rapid contraction. This paradigm is not followed during infection with virulent Salmonella typhimurium (ST), an intracellular bacterium that replicates within phagosomes of infected cells. While susceptible mice die rapidly (∼ 7 days), resistant mice (129X1SvJ) harbor a chronic infection lasting ∼60-90 days. Using recombinant Ovalbumin (OVA)-expressing ST (ST-OVA), I show that antigen-presentation is considerably delayed in mice infected with ST-OVA. Impairment of antigen-presentation by ST-OVA-infected macrophages and dendritic cells was not due to immuno-modulatory effects of ST virulence factors, because none of the mutants used in this study displayed enhanced priming. Instead, I propose that muted antigen presentation is a consequence of poor intracellular proliferation of ST and reduced antigen load. Proliferation of OVA-specific CD8+ T cells that were induced during infection peaked around day 21, and was followed by a prolonged phase of contraction. Furthermore, the magnitude of the response was contingent upon the extent of ST virulence. CD8+ T cell response against virulent ST displayed a prolonged and persistent effector-memory phenotype, while that against attenuated mutants displayed reduced numbers of effector-memory cells. Taken together, these results indicate that the muted and delayed activation of CD8+ T cells during infection with ST is mainly due to poor intracellular proliferation of ST, and that pathogen virulence influences the differentiation program of CD8+ T cells.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/28177 |
| Date | January 2009 |
| Creators | Albaghdadi, Homam |
| Publisher | University of Ottawa (Canada) |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 140 p. |
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