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

tel-00827710, version 1 - 29 May 2013
IFN is generated and found in the circulation after poly I:C injection (Figure 40).
Furthermore we had access to mice deficient for two major transcription factors, involved in
the expression of type I IFN: IRF3 and IRF7. These mice (IRF3/7 DKO) are unable to
produce type I IFN upon poly I:C injection (Figure 40). However it is important to note that
they are able to produce these cytokines after injection with other stimuli (Daffis et al., 2009).
Both the IFNAR -/- and the IRF3/7 DKO were compared to WT mice, which are able to
produce and to respond to type I IFN, for their ability to trigger a CD8 + T cell response.
As our main interest was to look at antigen-specific CD8 + T cells and the impact of type I IFN
on the outcome of the T cell response, we developed TCR-transgenic OT-I T cells that are
also IFNAR-deficient in order to have the capability to study the direct effect of type I IFN on
specific T cells.
Figure 40. Type I IFN production upon poly I:C stimulation. WT, IFNAR -/- and IRF3/7 DKO mice
received 100µg of poly I:C i.v. 6 hours later, plasma was collected and circulating IFNα concentration
was measured.
B. Inhibition of cross-priming upon early type I IFN production
We started by studying the mechanisms responsible for the inhibition of cross-priming upon
early delivery of poly I:C. Our goals were to determine which cells are the targets of poly I:C,
specifically focusing on the two main cell types implicated in cross-priming: DCs and CD8 + T
cells; whether the effects of poly I:C are type I IFN-dependent and, if that is the case, what are
the precise actions of type I IFN on its targets.
1) Type I IFN inhibit cross-priming through direct action on crosspresentation
Initially, we wanted to examine if the inhibition of cross-priming observed upon early poly
I:C injection was type I IFN-dependent. We started by testing the role of type I IFN in cross-
presentation. WT or IFNAR -/- recipient mice were immunized with K bm1 mOva splenocytes
Page 119 of 256