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

tel-00827710, version 1 - 29 May 2013
spleen (den Haan et al., 2000). In contrast, the latter subset was shown to specialize in MHC-
II antigen presentation (Dudziak et al., 2007). The same kind of dichotomy is true for
migratory DCs. CD103 + DCs performed more antigen cross-presentation while CD11b + DCs
are better for triggering CD4 help and humoral response stimulation (Bedoui et al., 2009).
(b) Cooperation between different DC subsets
Resident DCs in the spleen screen the blood for pathogens but also phagocytose materials that
are drained directly from the periphery through the lymphatic conduits. Migratory DCs
migrate to lymphoid organs upon activation where they can present antigen to specific T cells.
However, once they have arrived, they can transfer antigen to resident DCs that will present
antigen (Allan et al., 2006). Consequently the same antigen can be presented by different DC
subsets, with different specialization for antigen presentation (Belz et al., 2004).
(c) Ability to respond to different signals
Interestingly, DCs subsets display different patterns of PRR expression, resulting in
differential sensitivity to danger signals. In the spleen, the CD8α + DCs are the only subset to
express TLR3, but not TLR7, while the CD8α - subset is characterized by the opposite
phenotype (Edwards et al., 2003). These observations have important implications for
modulation of the immune response stimulated by PAMPs and for considering the appropriate
choice of adjuvants, which will be discussed later in this thesis.
3) Parallel between resident CD8α + DCs and migratory CD103 + DCs
To study the role of CD8α + DC subset in vivo, a mouse line lacking the transcription factor
Batf3 was developed. In these mice, this subset is missing and this knock-out has been
correlated with the absence of a protective CD8 + T cell response upon experimental West Nile
virus infection, as well as an inability to reject a syngeneic tumor (Hildner et al., 2008). These
results clearly demonstrated the crucial role of CD8α + DCs in cross-presentation.
Interestingly, the skin-resident CD103 + DCs are also absent in this mouse. These two subsets
share several common characteristics such as the expression of DEC205 or CD24, their cross-
presentation efficiency of both soluble and cell-associated antigens (den Haan et al., 2000)
(del Rio et al., 2007), and their ability to respond to the TLR3 ligand poly I:C (Schulz et al.,
2005; Sung et al., 2006). However, there are also differences: TLR3 was not detected in
CD103 + DCs and this subset does not seem as efficient as CD8α + DCs in promoting memory
CD8 + T cell responses. While they share several similarities, these 2 subsets are not identical
and, therefore, it was surprising that Batf3 would be critical for both DC populations.
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