Effect of IL10 on the immune system

Like most other cytokines, IL-10 exerts multiple effects upon the function of various cell lineages including lymphocytes, monocytes, natural killer (NK) cells, and dendritic cells.

T lymphocytes

In the mouse, IL-10 specifically inhibits TH1 cell cytokine synthesis (IFNy and IL-3) particularly when macrophages were used as antigen-presenting cells (APCs). IL-10 has been demonstrated to have inhibitory effects on the proliferation, survival and cytokine production of human T cells. In humans, direct interaction of IL-10 with the IL-10 receptor (IL-10R) on T cells results in specific suppression of IL-2 gene transcription thus inhibiting T cell proliferation. Since presence of IL-10 also reduces the expression of IL-2R on T cell clones, exogenous IL-2 cannot completely overcome the inhibition produced by IL-10. T Cells are also indirectly inhibited by IL-10 through alteration of the antigen-presenting function of monocytes. IL-10 accomplishes this effect by down regulating the expression of major histocompatibility complex (MHC) class II antigen on monocytes thus decreasing the peptide/MHC complexes available for interaction and adequate stimulation of T cells. Besides the effects on CD4 Th1 cells, IL-10 also inhibits IFNy synthesis by CD8 T cells without affecting their cytotoxic function. In contrast to these inhibitory effects, IL-10 also has positive effects where it can promote survival of II -2-starved T cells which otherwise are destined to undergo apoptosis. hIL-10 has also been shown to stimulate chemotaxis, proliferation, differentiation and cytolytic activity of human CD8+ T cells.

Macrophage/monocytes

Experimental evidence indicates that monocytes/ macrophages are the prime targets of IL-10 and has prominent effects on their morphology, phenotype and cytokine production. Besides causing dead-herence and rounding up of monocytes, IL-10 also strongly inhibits their constitutive and inducible expression of MHC class II antigen. IL-10 also has the ability to block B7 and ICAM-1 expression in monocytes in response to IFNy, thereby disrupting monocyte-T cell interaction. Production of IL-la, IL-ip, IL-6, IL-8, tumor necrosis factor a (TNFa), granulocyte-macrophage (GM-) and granulocyte colony-stimulating factor (G-CSF) by human monocytes following activation is inhibited by IL-10 at the mRNA and protein level. IL-10 also prevents IL-12 expression from monocytes, thereby inhibiting T,,l cell development. Furthermore, IL-10 inhibits its own production by monocytes indicating the presence of a self-regulatory negative feedback loop.

Natural killer (NK) cells

IL-10 can inhibit monocyte-induced NK cells production of IFNy. IL-10 has this effect on NK cells indirectly by suppressing monocyte production of IL-12. However production of IFNy, TNFa and GM-CSF by IL-2-activated NK cells is significantly enhanced by IL-10. IL-10 has also been shown to induce significant NK cytotoxic activity against NK-resistant tumor cell targets.

B lymphocytes

Unlike the effects on monocytes, IL-10 induces the expression of MHC class II antigen on resting B cells. IL-10 leads to enhanced viability of B cells in vitro and augments their differentiation into antibody-secreting cells particularly after activation by anti-CD40 antibody. IL-10 synergizes with IL-2 to induce B cell differentiation by upregulating their high-affinity IL-2 receptor. Upon stimulation with polyclonal activators or transformation by EBV, purified B cells will produce IL-10. The ability of B lymphocytes to produce and to respond simultaneously to II.-IO has suggested that this cytokine may act as an autocrine growth factor in humans.

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