During this program, we have successfully developed an innovative miniaturized in vitro co-culture system to systematically interrogate the dialogue between various type of innate immune cells (which are immune sensors detecting the first events of an infection), and memory T cells.
We used this experimental system in the context of Influenza A virus infection. We chose Influenza A virus as a model because it triggers strong innate immune responses and generates memory T cells that we can use as a functional readout in our experimental approaches. We were then able to characterize and systematically compare the diversification of several innate immune cell subsets in response to Influenza challenge (i.e. expression of immune checkpoints proteins and secretion of cytokines). In addition, by comparing the different innate immune cells for their ability to reactivate memory T cells, we uncovered the important role of a particular innate immune cell subset that induces higher functional activation and proliferation rate of memory T cells, as compared to the other innate cells. These results are important as this innate cell subset could be targeted by next-generation vaccines in order to stimulate memory T cells. We are currently extending those results by the analysis of the gene expression and the clonal diversity of the memory T cells, in order to determine the molecular mechanisms leading to their functional activation and proliferation.
As of today, we have presented these results at several seminars and scientific gatherings, and several original publications are currently under preparation.
