Characterization of Foxp3+CD4+CD25+ and IL-10-Secreting CD4+CD25+ T Cells during Cure of Colitis

Abstract

CD4+CD25+ regulatory T cells can prevent and resolve intestinal inflammation in the murine T cell transfer model of colitis. Using Foxp3 as a marker of regulatory T cell activity, we now provide a comprehensive analysis of the in vivo distribution of Foxp3+CD4+CD25+ cells in wild-type mice, and during cure of experimental colitis. In both cases, Foxp3+CD4+CD25+ cells were found to accumulate in the colon and secondary lymphoid organs. Importantly, Foxp3+ cells were present at increased density in colon samples from patients with ulcerative colitis or Crohn’s disease, suggesting similarities in the behaviour of murine and human regulatory cells under inflammatory conditions. Cure of murine colitis was dependent on the presence of IL- 10, and IL-10-producing CD4+CD25+ T cells were enriched within the colon during cure of colitis and also under steady state conditions. Our data indicate that although CD4+CD25+ T cells expressing Foxp3 are present within both lymphoid organs and the colon, subsets of IL- 10-producing CD4+CD25+ T cells are present mainly within the intestinal lamina propria suggesting compartmentalization of the regulatory T cell response at effector sites.

Intratumor OX40 stimulation inhibits IRF1 expression and IL‐10 production by Treg cells while enhancing CD40L expression by effector memory T cells

“…IL-10 is one of the best-known cytokines endowed with immune-suppressive functions. Il10 gene expression characterizes Treg-cell signature [30], even though a significant IL-10 expression at the protein level can be detected in naïve mice only in the intestine [15,31]. Treg-cellderived IL-10 is redundant for the control of systemic autoimmunity but becomes crucial for the control of inflammation at the mucosal interfaces with the external environment, such as in lungs and colon [32].…”

“…Treg cells secrete interleukin 10 (IL-10), which plays a critical role in suppressing immune responses and in particular the maturation of fully competent DCs [13][14][15]. Among tumor-infiltrating Teff cells, the subpopulation of effector memory T (Tem) cells is the most abundant.…”

Is FOXP3 a bona fide marker for human regulatory T cells?

“…In addition, it cannot be excluded that Tr1 cells require FOXP3 to exert their suppression in vivo. Indeed, in a preclinical model of inflammatory bowel disease, Treg expressing FOXP3 and secreting IL-10 are selectively localized in the intestinal lamina propria where they suppress Teff cells responses [32]. The origin of these cells is not clear.…”

The role of T‐regulatory cells and Toll‐like receptors in the pathogenesis of human inflammatory bowel disease

“…5,6 Pioneering experiments by Powrie et al demonstrated, more than 15 years ago, that transfer of naive CD4 + T cells into immunodeficient mice in the absence of Treg cells results in colitis that is dependent on the presence of commensal bacteria. [7][8][9] Remarkably, adoptive transfer of Treg cells not only prevents disease, but also, acting through both IL-10 and transforming growth factor-b (TGF-b)-dependent and -independent mechanisms, halts the progression of established disease and reverses pathology.…”