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

tel-00827710, version 1 - 29 May 2013
This high background may prevent the visualization of a small increase in these conditions.
Repeating this experiment using alternative restimulation strategies, or analysis at earlier time
points is required to validate these results.
Figure 48. Type I IFN has a limited action on antigen-specific T cells. 5x10 3 CD45.1/2 WT OT-I
and 5x10 3 CD45.2/2 IFNAR -/- OT-I were transferred into IFNAR -/- CD45.1/1 recipients. The day after,
mice were immunized i.d. with 5x10 5 K bm1 mOva splenocytes. They received 100µg of poly I:C on day
3. On day 7, enrichment was performed using a CD45.2 antibody to detect the 2 populations of OT-I.
After ex vivo restimulation, IFNγ intracellular staining was done. The percentages of WT and IFNAR -/-
CD8 + OT-I cells producing IFNγ (A) as well as the geometric fluorescent mean for IFNγ (B) are
reported.
Together these data demonstrate that the timing-dependent differential effects of poly I:C are
at least partially type I IFN-dependent. This adjuvant clearly acts at the level of antigen-
presenting DCs by modulating their survival and/or migration, maturation state, ability to
cross-present antigen and even the persistence of antigen inside them. Type I IFN might also
play a critical role at the level of responding T cells but additional work will be needed to
confirm this.
III. HOW TO CHOOSE THE OPTIMAL TIMING FOR ADJUVANT
DELIVERY?
Our data demonstrate that the optimal timing for adjuvant delivery is dependent on the route
of immunization. We first showed that the early administration of adjuvant abrogates
subsequent cross-priming (I). These results were followed by a more detailed study that
attempted to understand the mechanisms underlying the differential effects of poly I:C and
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