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

tel-00827710, version 1 - 29 May 2013
They also showed differences in the corresponding responses, but in a different manner: in
their hands, the magnitude and the secondary response of the CD8 + T cells were affected by
the duration of antigenic stimulation, but not the functionality of effector cells (Prlic et al.,
2006). In another model, the authors blocked antigen presentation by using anti-K b -
SIINFEKL MHC-peptide complexe antibody in order to assess the effect of modulating the
duration of MHC-peptide complexe signaling on T cell responsiveness. They demonstrated
that altering this interaction affected both T cell expansion and the differentiation into
memory T cells (Obar and Lefrancois, 2010). Interestingly, different and sometimes even
opposite results have been reported in answer to these questions, seemingly dependent on the
model used to modulate antigen persistence.
Based on our results about persistence of antigen and its relation to cross-presentation, we can
consider, for our comparisons, the i.v. condition as a brief stimulation and the i.d. condition as
sustained antigen stimulation (Figure 32, cohort 3). We observed a similar expansion of T
cells in both conditions, but a qualitatively better primary response and a more robust
secondary response after a sustained stimulation. These results are in accordance with
previous papers showing that the duration of antigenic stimulation can impact CD8 + T cell
differentiation.
However, different and even opposite results have also been described depending on the
model used to modulate antigen persistence. Another approach used in our lab to modulate
persistence of antigen has also led to controversial results. Previous work in our lab,
comparing cross-priming after immunization with WT or β2m -/- splenocytes demonstrated
that persistence of antigen is crucial for efficient priming. Indeed β2m -/- are rapidly killed by
NK cells, resulting in their removal. Cross-priming is much more efficient after immunization
with WT than β2m -/- splenocytes, suggesting that the ability of the WT cells to stay in the
tissue contributed to the increased efficiency of cross-priming. Furthermore, efficient cross-
priming was restored in the β2m -/- immunization conditions, but only if NK cells were
depleted, allowing for the β2m -/- cells to persist (Jusforgues-Saklani et al., 2008). In contrast,
Krebs and colleagues demonstrated the opposite effects of NK killing in an Ovalbumin
model. They immunized mice with K b-/- mOva splenocytes that are also targets for NK cells.
However, in this setting, they observed more efficient priming when NK cells were present,
suggesting a role for NK cells in the killing of cell-associated antigen and providing antigen
to APCs (Krebs et al., 2009).
From the results described here we can conclude that the model used to study antigen
persistence is a critical factor to take into account when studying the modulation of T cell
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