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

tel-00827710, version 1 - 29 May 2013
of monocytes into DCs with varying phenotypes and functions. Activation of monocytes with
IL-4, IFNα, TNF or IL-15 gave rise to different populations of DCs with diverse phenotypes.
That could explain the different efficiencies of these cells in mounting CD8 + T cell responses
(Paquette et al., 1998; Dubsky et al., 2007).
(b) Side effects of type I IFN treatment on DCs
Not all type I IFN effects on DCs promote a well-regulated immune response. Autoimmune
disorders have been observed in melanoma patients undergoing treatment with type I IFN.
One hypothesis is that IFN induced in vivo maturation of DCs that have taken up self-antigen
and this led to an autoimmune response (Rizza et al., 2010).
(c) Targeting DCs with specific antigens
It was previously introduced that the type of antigen and thus the type of receptor implicated
for antigen uptake plays a role in the efficiency of the subsequent immune response. One
promising approach for vaccination development is to target antigens to a specific subset of
DCs by coupling them with antibodies directed against DC-specific cell-surface molecules.
The CD8α + DC subset has been the most studied thus far, due to its specialization for cross-
priming. Antibodies coupled to Ovalbumin and targeting different receptors, DEC-205,
Clec9A and Clec12A were tested. Interestingly it was observed that the outcome of the
response and the requirement for adjuvant depends on which receptor was targeted. DEC-205
and Clec9A are effective targets to promote cytotoxic T cell responses, while Clec12A was
shown to be inefficient (Lahoud et al., 2011). Addition of adjuvant is always required to
induce a CD8 + T cell response. In contrast, a potent humoral response can be obtained upon
targeting of antigen to Clec9A in the absence of adjuvant (Figure 56). Since Clec9A
expression is restricted to CD8α + DCs and pDCs, this observation may be due to a longer
persistence of antigen coupled to antibody in the blood because fewer cells are available that
can endocytosed it, allowing for a sustained presentation on MHC-II.
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