Voie d'immunisation et séquence d'administration de l ... - TEL

tel-00827710, version 1 - 29 May 2013
compared to the antigen administered alone. Although the adjuvant theorically could still
promote the immune response further, the lack of this effect is most likely due to being past
the time point when type I IFN has already acted to promote antigen survival and processing.
Interesting results have also been obtained regarding the effects of poly I:C and type I IFN
effects at the level of CD8 + T cells. Several groups have demonstrated a direct effect of type I
IFN on T cells (Le Bon et al., 2006; Kolumam et al., 2005). Additionally, Marshall and
colleagues studied the effects of type I IFN released after viral infection on bystander T cells
that are not specific for the viral antigens. They demonstrated that type I IFN sensitize
bystander T cells, leading to enhanced effector functions, such as IFNγ secretion, upon
stimulation with their cognate antigen. Similar effects were observed after poly I:C
administration and prior to immunization with antigen. It was shown that these effects were
also due to IFN, acting indirectly on bystander T cells (Marshall et al., 2010). In a follow-up
study, the same group observed that IFN released upon viral infection or poly I:C treatment
resulted in a transient immunosuppression and inhibition of T cell proliferation depending on
the timing of its stimulation and production. Likewise, IFN was able to act as a stimulatory
adjuvant when bystander T cells were exposed to the inflammatory milieu and cognate
antigen at the beginning of type I IFN production, whereas an immunosuppressive effect on T
cell proliferation was observed when T cells encountered the antigen after prior exposure to
type I IFN (Marshall et al., 2011). These mechanisms may also play a role in our model and
contribute to the pleiotropic roles of poly I:C and downstream type I IFN production on cross-
priming.
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