Large intestine intraepithelial lymphocytes from Apc+/+ and Apc+/Min mice and their modulation by indigestible carbohydrates: the IL-15/IL-15R alpha complex and CD4+ CD25+ T cells are the main targets.

Abstract

We have shown recently that some indigestible carbohydrate (short-chain fructo-oligosaccharides [sc-FOS]) reduced colon tumor incidence in Apc+/Min mice, and that this effect depended on a functional local immune system. In addition, IL-15 mRNA was concomitantly modulated in the mucosa. Since intraepithelial lymphocytes (IELs) are in close contact with intestinal epithelial cells, these cells are the candidates most likely to be involved in early cancer immunosurveillance. The present study documents the effects of sc-FOS on large intestine IELs (LI-IELs) from Apc+/+ or Apc+/Min mice by analyzing markers related to their phenotype, their activation status, and the cell surface IL-15/IL-5R alpha. In the colons of Apc+/Min mice, fewer LI-IELs expressed surface IL-15/IL-15R alpha. In addition, a lower number of CD4+ LI-IELs expressed CD25, although more LI-IELs expressed CD69, as compared to normal mice. The sc-FOS enriched diet caused a decrease in the proportion of CD25+ LI-IELs and an increase in the percentage of LI-IELs bearing surface IL-15/IL-15R alpha, independently of the Apc gene status. The IL-15/IL-15R alpha increase was, however, higher in Min mice, and returned to a level very similar to that of Apc+/+ mice when the latter mice were fed a low-fiber diet. The sc-FOS-enriched diet specifically induced an increase in CD69+ cells in Apc+/+ mice, and a decrease in the proportion of CD4+ CD25+ LI-IELs in Apc+/Min mice. Some of these modulations could contribute to the development of a better immune anticancer response in the early steps of cancer development.