Antigen Requirements for Efficient Priming of CD8+T Cells byLeishmania major-Infected Dendritic Cells

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Abstract
CD4+and CD8+T-cell responses have been shown to be critical for the development and maintenance of acquired resistance to infections with the protozoan parasiteLeishmania major. Monitoring the development of immunodominant or clonally restricted T-cell subsets in response to infection has been difficult, however, due to the paucity of known epitopes. We have analyzed the potential ofL. majortransgenic parasites, expressing the model antigen ovalbumin (OVA), to be presented by antigen-presenting cells to OVA-specific OT-II CD4+or OT-I CD8+T cells. Truncated OVA was expressed inL. majoras part of a secreted or nonsecreted chimeric protein withL. donovani3′ nucleotidase (NT-OVA). Dendritic cells (DC) but not macrophages infected withL. majorthat secreted NT-OVA could prime OT-I T cells to proliferate and release gamma interferon. A diminished T-cell response was observed when DC were infected with parasites expressing nonsecreted NT-OVA or with heat-killed parasites. Inoculation of mice with transgenic parasites elicited the proliferation of adoptively transferred OT-I T cells and their recruitment to the site of infection in the skin. Together, these results demonstrate the possibility of targeting heterologous antigens to specific cellular compartments inL. majorand suggest that proteins secreted or released byL. majorin infected DC are a major source of peptides for the generation of parasite-specific CD8+T cells. The ability ofL. majortransgenic parasites to activate OT-I CD8+T cells in vivo will permit the analysis of parasite-driven T-cell expansion, differentiation, and recruitment at the clonal level.

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