Total parenteral nutrition-associated changes in mouse intestinal intraepithelial lymphocytes.

Intraepithelial lymphocytes (IEL) play a major role in mucosal defense mechanisms against intraluminal foreign antigens. To address the role luminal nutrients have on the phenotype and function of the IEL, we administered total parenteral nutrition (TPN) to mice, with the absence of enteral intake. We hypothesized that administration of TPN would result in changes in the phenotype and function of the IEL. For this, we utilized a mouse model of TPN. A significant decline in the CD4+ IEL population occurred with TPN. Additionally, the CD8+,CD44+ IEL subset showed a 65% decline (P < 0.05), and the CD4+,CD44+ subset declined by 55% with TPN (P < 0.05). The CD8alphabeta+ population (a marker of thymic-dependence) also declined by 92% (P < 0.01) with TPN. IEL in the TPN group showed a significantly lower degree of in vitro proliferation. In conclusion, the IEL showed significant phenotypic changes with TPN including the loss of the thymic-derived population. Functionally, the IEL showed a significant decline in proliferation. Such changes demonstrate the important role luminal nutrients have on IEL phenotype and function.

Interferon-gamma expression by intraepithelial lymphocytes results in a loss of epithelial barrier function in a mouse model of total parenteral nutrition.

OBJECTIVE: To determine the etiology of the loss of epithelial barrier function observed with the administration of total parenteral nutrition (TPN) in a mouse model. SUMMARY BACKGROUND DATA: Removal of enteral nutrition with the administration of TPN is associated with a loss of intestinal epithelial barrier function. The etiology of this barrier loss is not clear. Because intraepithelial lymphocytes (IELs) produce a number of cytokines that may alter epithelial permeability, the authors investigated IEL cytokine expression in a mouse model of TPN. METHODS: Adult C57BL/6 mice received TPN or enteral diet for 7 days. IELs were subsequently harvested and the mRNA expression of cytokines was measured. Epithelial barrier function was assessed in vitro with 51Cr-EDTA in Ussing chambers and was expressed as the permeability coefficient (Papp). RESULTS: IEL mRNA expression of interferon-gamma (IFN-gamma) rose from 0.14 +/- 0.07 in the control (enterally fed) group to 0.44 +/- 0.11 attomoles/microL in the TPN group (P <.05). Transforming growth factor-beta1 declined slightly but not significantly, from 0.75 +/- 0.35 to 0.55 +/- 0.18 attomoles/microL in the control and TPN groups, respectively. Epithelial barrier function declined significantly with TPN compared to controls. To assess the relevance of IFN-gamma changes, permeability in IFN-gamma knockout mice was studied. Barrier function was significantly higher in IFN-gamma knockout mice on TPN compared to C57BL/6 mice that received TPN. CONCLUSIONS: IEL cytokine expression changes significantly with TPN administration. The partial correction with IFN-gamma knockout mice suggests that an upregulation of IFN-gamma expression is one mechanism responsible for the loss of the epithelial barrier associated with TPN.