: Dendritic cells (DC) are specialized antigen presenting cells that stimulate very potent responses in both naive and memory T lymphocytes. They can prime CD4+ and CD8+ T cell responses against antigens that are poorly immunogenic using more conventional immunization strategies, and show particular promise for vaccination against tumor antigens. Mice immunized with DC pulsed with peptides defining class I-restricted epitopes develop CD8+ T cell memory that persists for more than a year. Successful priming is critically dependent on help from CD4+ T cells that recognize antigen on the same DC. Several groups have recently shown that cross-linking CD4O on the DC can substitute for CD4 T cell help. DC infected with viruses can also stimulate CD8+T cells in the absence of CD4+ T cells via a CD4O-independent mechanism. CD4+ T cell help is also essential for the maintenance of CD8+ T cell memory in individuals with chronic virus infection, and is also important for effective vaccination to tumor antigens. The experiments in this proposal will investigate the basic immunology of CD8+ memory responses primed by immunization with DC. There are three major aims. First, what mechanisms contribute to the successful priming of CD8+ memory by DC? Second, how can manipulation of CD4+ T cell help influence the generation of CD8+ T cell memory? Third, how effectively can DC prime CD8+ T cell memory in the absence of CD4+ T cell help? These questions will be addressed using single cell assays for cytokine production, and adoptive transfer of T cell receptor transgenic CD8+ T cells to analyze cell division, expression of cell surface markers, and cytokine synthesis.
|Ontiveros, Fernando; Wilson, Elizabeth B; Livingstone, Alexandra M (2011) Type I interferon supports primary CD8+ T-cell responses to peptide-pulsed dendritic cells in the absence of CD4+ T-cell help. Immunology 132:549-58|
|Livingstone, Alexandra M; Wilson, Elizabeth B; Ontiveros, Fernando et al. (2009) Unravelling the mechanisms of help for CD8+ T cell responses. Immunol Res 45:209-17|
|Wilson, Elizabeth B; Livingstone, Alexandra M (2008) Cutting edge: CD4+ T cell-derived IL-2 is essential for help-dependent primary CD8+ T cell responses. J Immunol 181:7445-8|
|Wang, Jyh-Chiang E; Livingstone, Alexandra M (2003) Cutting edge: CD4+ T cell help can be essential for primary CD8+ T cell responses in vivo. J Immunol 171:6339-43|