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

tel-00827710, version 1 - 29 May 2013
responses. Building upon these conclusions, type I IFN are now commonly used for DC
immunotherapy to induce DC differentiation and maturation (Santini et al., 2000).
(iii) Persistence of antigen
Lorenzi and colleagues have analyzed the effects of type I IFN on cross-presentation by using
UV irradiation-induced apoptotic EG7 thymoma cells in combination with type I IFN, both in
vitro and in vivo (Lorenzi et al., 2011). They demonstrated that type I IFN do not actually
affect the uptake of antigen by DCs but, rather, enhance the retention of engulfed antigen
inside of DCs, probably in phagosomal compartments. Moreover, they showed that this was
most likely due to the regulation of phagosomal pH by type I IFN (Figure 12).
Figure 12. Multiple sources and multiple targets of type I IFN.
(c) Effects of type I IFN on T cells
Type I IFN not only modulate the DC life cycle and responsiveness, but also appear to play a
critical role in many events surrounding T cell survival, activation and responsiveness
(Figure 12).
(i) T cell survival
It has been shown that type I IFN act to promote the survival of WT but not IFNAR-deficient
T cells, indicating that IFN signaling is critical in this process (Marrack et al., 1999). This
function for these cytokines is thought to help in avoiding the rapid death of antigen-specific
T cells upon antigenic stimulation.
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