The presence of long-lasting CD8 T cell memory is crucial for protection against re-infection by many pathogens. For this reason, vaccination must aim to generate CD8 memory T cells. However, at present the generation of such cells is only achieved by vacc ination with live vaccines. These vaccines utilize attenuated viral strains which can be very difficult to generate and which can present safety hazards. Therefore, it is important to identify new ways of making safe vaccines able to generate strong CD8 me mory cells against soluble proteins. We have previously shown that we can generate strong primary CD8 responses against soluble proteins by co-administrating a natural adjuvant, IFN-a/b. These responses are generated by cross-priming and are independent of CD40. However before this approach can be applied to the development of new vaccines, some fundamental questions must be addressed. The aim of this project is to address the most important of these questions:1)To characterize, in depth CD8 memory cells ge nerated against soluble proteins by cross-priming compared to those generated after viral or bacterial infection against the same antigen2) To study the effect of antigen localisation on the development of memory CD8 T cells. The effect of the route of imm unization on the development of subsequent memory CD8 T cells will be evaluated.3) To identify the subsets as well as the activation status of dendritic cells required for the generation of long-lasting CTL responses.4) To study the effect of the tissue-or igin of the DC in the imprinting of the memory cells All together, this project should allow a better understanding of how to generate potent memory cells by cross-priming as well as providing some insights of the conditions in which dendritic cells can al low the generation of memory cells.
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