CD4+CD25+ regulatory T cells have divergent effects on intestinal inflammation in IL-10 gene-deficient mice.

The regulatory effect of murine CD4+CD25+ T-cells in vivo appears to be dependent on the secretion of IL-10. The lack of IL-10 in the IL-10 gene-deficient mouse has a profoundly negative effect on the mouse's regulation of the response to intestinal bacteria, resulting in severe enterocolitis. We investigated the effect of neonatal injection with wild-type CD4+CD25+ T-cells on the intestinal immune response in IL-10 gene-deficient mice.

A defect in epithelial barrier integrity is not required for a systemic response to bacterial antigens or intestinal injury in T cell receptor-alpha gene-deficient mice.

Background And Aims: Genetically induced disruption of the intestinal epithelial barrier leads to development of intestinal inflammation. In the interleukin-10 gene-deficient inflammatory bowel disease (IBD) mouse model, for instance, a primary defect in intestinal epithelial integrity occurs before the development of enterocolitis. In humans, a causal role for epithelial barrier disruption is still controversial.

Association with selected bacteria does not cause enterocolitis in IL-10 gene-deficient mice despite a systemic immune response.

Resident bacteria have been implicated to play a major role in the development of inflammatory bowel disease. While luminally sterile IL-10 gene-deficient mice remain disease-free, their conventionally raised littermates develop enterocolitis associated with increased numbers of luminal and mucosal adherent bacteria. To investigate the role of defined bacteria on the initiation and development of this enterocolitis, we associated luminally sterile IL-10 gene-deficient mice with pure strains of resident bacteria.

Lack of interleukin-10 leads to intestinal inflammation, independent of the time at which luminal microbial colonization occurs.

Previous studies have demonstrated that the resident bacteria harbored by interleukin (IL)-10 gene-deficient mice initiate an enterocolitis in the neonatal period. The associated intestinal injury is characterized by an increase in the secretion of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, and by a systemic response to endogenous bacterial antigens, supporting the hypothesis that a lack of tolerance may be the initiating cause. Whether bacterial initiation of this enterocolitis would occur in the adult intestine or whether it is only seen in the developing neonatal intestine was not known.

Normal Breast Milk Limits the Development of Colitis in IL-10-Deficient Mice.

Background And Aims: This study examined the role of breast milk in neonatal bacterial colonization of the colon and disease progression in IL-10-deficient mice.

Methods: IL-10-deficient mice were cross-fostered at birth and raised until weaning with a normal mother. Results were compared with normal pups cross-fostered to an IL-10-deficient mother.