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

tel-00827710, version 1 - 29 May 2013
(ii) T cell migration and recirculation
It has been shown that type I IFN are capable of modulating T and B cell recirculation by
inducing the redistribution of lymphocytes throughout the body. Treatment with type I IFN
triggers a transient blood lymphopenia, which occurs through the direct stimulation of
lymphocytes (Kamphuis et al., 2006). Type I IFN also improve T cell priming by facilitating
the encounter between antigen-presenting DCs and T cells in the draining lymph node. To
accomplish this, type I IFN have been shown to induce the retention of T cells in the lymph
node by downregulating the expression of sphingosine-1-phosphate (Shiow et al., 2006),
increasing the probability that DCs will encounter the antigen- specific T cells.
(iii) CD8 + T cell activation and differentiation
Type I IFN have been described to act as a potential “signal 3” in the activation cascade
needed for CD8 + T cell stimulation by antigen-presenting DCs (Curtsinger et al., 2005).
While Le Bon et al. initially showed that the enhancement of CD8 + T cell cross-priming is
exclusively due to a direct action of type I IFN on DCs, they further demonstrated a few years
later that IFN are additionally acting at the level of the CD8 + T cell. To do this, they used a
mixed BM-chimera model where the T cell population was deficient for IFNAR. In these
animals, they observed an overall reduction in effective priming (Le Bon et al., 2006). These
results were confirmed by another group using the transfer of antigen-specific CD8 + T cells
into either WT or IFNAR -/- mice to show that the T cells are actually the direct targets of type
I IFN and that these cytokines have a direct impact on both T cell clonal expansion and
memory formation (Kolumam et al., 2005; Thompson et al., 2006).
(iv) CD4 + T cell differentiation
Type I IFN also modulate the differentiation of CD4 + T cells. They have been shown to favor
Th1 differentiation, when signaling in combination with other cytokines such as IL-12. By
contrast, they inhibit T cell differentiation into the Th2 or Th17 subsets, which have been
implicated in allergies and inflammatory responses (Huber and Farrar, 2011).
(d) Effects of type I IFN on other immune cells
Type I IFN have also been implicated in the regulation of other leukocytes (Figure 12). In
particular, type I IFN are known to activate NK cells by enhancing their cytolytic activity and
production of IFNγ. Moreover they also induce the accumulation of proliferating NK cells via
induction of the main NK-regulatory cytokine, IL-15 (Nguyen et al., 2002). Beyond
lymphocytes, type I IFN is also known to boost macrophage activity (Bogdan et al., 2004).
68