Dendritic Cells

It is universally acknowledged that T cells activity is strictly dependent upon their interaction with dendritic cells (DC).59 Therefore, it is not surprising that IL-10 immunosuppressive effects on T cells are believed to be largely mediated by the effects of this cytokine on DC.60-63 IL-10 impairs the antigen presenting properties of DC by reducing their expression of HLA

class II molecules,64'65 intercellular adhesion molecules (e.g., ICAM-1)66,67 and costimulatory molecules68-71 (i.e., CD80/B7- 1 and CD86/B7.2), which correlates with its ability to impair primary alloantigen-specific T cell responses.23 24 Of note, as class I HLA expression by DC is not reported to be downregulated by IL-10,66 cross priming of CTL might not be as much affected by this cytokine as it is that of CD4+ T cells.

These observations have been extended to different experimental models and have shown that IL-10-conditioned DC can induce a state of anergy in alloantigen- or peptide-activated T cells.22,40,72-76 Finally, like T cells, DC can be the target of but also produce IL-10.77,78 In particular, it has been proposed that IL-10-producing DC may be involved in the generation of T regulatory cells with immunosuppressive function (see below).

Although the inhibition of antigen presentation is a well documented result of IL-10 activity on DC, antigen uptake by APC appears to be promoted by this cytokine.79,80 This, combined with the IL-10 induced inhibition of DC migration,81-83 might represent an important function of IL-10 in an early phase of DC maturation, when immature DC must accumulate in the relevant arena and be loaded with antigens from damaged tissues.

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