Type I IFN (IFN) are innate cytokines produced by host cells during viral infection. Ithas pleiotropic and sometimes opposing, protective or detrimental effects, on both innateand adaptive immunity that remain poorly understood. Parts of IFN response may be explain by intrinsic effect (cell-‐specificity). My thesis was focused on the effect of the microenvironment, as present during T Helper cell differentiation, on IFN response. Using a systems level approach, we studied IFN responses during Four Human T Helper cell differentiation. We identified 1/ a conserved IFN-‐induced transcriptional program comprising mostly antiviral genes 2/ a flexible IFN response, leading to a different pattern of chemokine and cytokine induction by IFN in distinct Th environments. Antiviral response was also flexible with a lesser protection to HIV-1 and HIV-2 infection in Th2 and Th17 contexts. Our in vitro results suggested that environmental control might shape the effects of IFN in different physiopathological contexts.
