Objective
The aim of this project is to dissect the cellular basis of immunological memory in. order to provide rationale approach to vaccination, so far only developed on an empirical basis. To this end, we will make use of recently identified memory lymphoid subset markers and recent technological breakthroughs permitting isolation of cells with defined effectors functions and antigen specificities to investigate the mechanisms that generate and maintain different types of memory cells. The relative role of tissue homing effectors memory T cells versus lymph node homing central memory T cells will be studied and the latter will be analysed to identify the cells that in secondary responses serve as precursors for effectors, help B cells, or mediate immune suppression. The analysis will be extended ton on-conventional NK-T and god T cells. The contribution of memory B cells and short-and long-lived plasma cells in protective and reactive memory responses will be analysed. The knowledge acquired through the above in vitro systems will be applied to the assessment of memory responses in vivo in rodent models and in primates immunized with hepatitis C virus-derived antigens. These results are expected to provide new general insights into the mechanisms of immunological memory and to identify immune parameters correlating with protective responses following viral infections.