Cancer Immune Therapy Edited by G. Stuhler and P. Walden ...

inhibits the capacity of monocytes and macrophages to present antigen to T cells.
This is realized by down-regulation of constitutive and IFN-g-induced cell surface levels
of MHC class II, of co-stimulatory molecules like CD86 and of some adhesion
molecules such as CD58 [47±49]. In addition, IL-10 inhibits the monocytic production
of IL-12, an essential mediator for the development of specific cellular immune defense
[50]. On the other hand, IL-10 favors the phagocytic activity of monocytes and
macrophages [51]. This is realized among others by up-regulated expression of specific
receptors that mediate the uptake of opsonized and non-opsonized microorganisms.
In fact, IL-10-treated monocytes and macrophages show an enhanced expression
not only of IgG Fc receptors (CD16, CD32 and CD64) but also of scavenger receptors
like CD163 and CD14 [52±55]. Interestingly, IL-10 simultaneously diminishes
the killing of ingested microorganisms [56]. The up-regulated expression of scavenger
receptors is probably responsible for the observation that IL-10-treated monocytes
and macrophages strongly ingest apoptotic cells (W.-D. Dæcke and R. Sabat, unpublished).
The chemotaxis of monocytes is only weakly impaired by IL-10 [57].
8.3.2
Effectson T Cells
8.3 Biological Activities of IL-10
As well as the dominating indirect impact via APCs, IL-10 also exerts a direct effect
on T cells (Fig. 8.1). In particular, inhibitory effects have been described on CD4 + T
cells. IL-10 inhibits the proliferation as well as the cytokine synthesis of these cells.
Concerning the latter, it affects their IL-2 and IFN-g as well as their IL-4 and IL-5 production
as induced by various stimuli [58, 59]. At least in the human system, IL-10
therefore seems to inhibit both the Th1- and Th2-type responses, though the effect on
Th1 cells appears to be stronger [60]. The influence of IL-10 on CD4 + T cells is particularly
marked on the naive cells. Activated and memory T cells seem to be rather in-
Fig. 8.1 Effects of IL-10 on APC±T cell interaction. IL-10 suppresses the
expression of pro-inflammatorycytokines and enhances the formation of
anti-inflammatorymediators. Moreover, IL-10 inhibits the capacityof
monocytes and macrophages to present antigen to T cells. (see color
plates page XXV)
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