An Essential Role for Interleukin 10 in the Function of Regulatory T Cells That Inhibit Intestinal Inflammation

Abstract

A T helper cell type 1–mediated colitis develops in severe combined immunodeficient mice after transfer of CD45RBhigh CD4+ T cells and can be prevented by cotransfer of the CD45RBlow subset. The immune-suppressive activities of the CD45RBlow T cell population can be reversed in vivo by administration of an anti-transforming growth factor β antibody. Here we show that interleukin (IL)-10 is an essential mediator of the regulatory functions of the CD45RBlow population. This population isolated from IL-10–deficient (IL-10−/−) mice was unable to protect from colitis and when transferred alone to immune-deficient recipients induced colitis. Treatment with an anti–murine IL-10 receptor monoclonal antibody abrogated inhibition of colitis mediated by wild-type (WT) CD45RBlow CD4+ cells, suggesting that IL-10 was necessary for the effector function of the regulatory T cell population. Inhibition of colitis by WT regulatory T cells was not dependent on IL-10 production by progeny of the CD45RBhigh CD4+ cells, as CD45RBlow CD4+ cells from WT mice were able to inhibit colitis induced by IL-10−/− CD45RBhigh CD4+ cells. These findings provide the first clear evidence that IL-10 plays a nonredundant role in the functioning of regulatory T cells that control inflammatory responses towards intestinal antigens.

Immune Modulation and Prevention of Autoimmune Disease by Repeated Sequences from Parasites Linked to Self Antigens

“…These cytokines are important in cell mediated suppression and crucial in the generation of regulatory FoxP3+ T cells (Powrie et al, 1996;Asseman et al, 1999;Maloy and Powrie, 2001;Green et al, 2003). The impact of IL-10 and TGF-β on the suppressive function mediated by the SAg fusion constructs in the EAE model was investigated by neutralization of cytokines.…”

Regulation of CD4+CD25+ regulatory T cell activity: it takes (IL‐)two to tango

“…Also, Treg isolated from secondary lymphoid organs of normal mice do not produce IL-10 or TGF-b upon re-stimulation. In contrast, there is evidence that IL-10 and TGF-b may be relevant mediators of suppression in vivo [6][7][8][9][10][11] and Treg isolated from sites of active immune reactions are able to produce high amounts of IL-10 upon re-stimulation [7,11,12]. Recent data indicate that IL-2 is critical for the activation of Treg effector function, such as production of IL-10.…”

Certified Professionals

“…In contrast to the lack of involvement of cytokines in CD25 + -mediated suppression in vitro, IL-10, IL-4, and TGF-β have been implicated as mediating suppression of some 22 23 24, but not all (25, and unpublished observations), autoimmune diseases by Tr cells. While IL-10 is produced by the Tr cells 24, it has not yet been shown that IL-4 or TGF-β are actually produced by CD25 + regulatory cells in vivo.…”

“…While IL-10 is produced by the Tr cells 24, it has not yet been shown that IL-4 or TGF-β are actually produced by CD25 + regulatory cells in vivo. Thus, it is difficult to conclude if these cytokines are responsible for the suppressive effects of the Tr cells or if they play a role in the differentiation of the Tr cells.…”