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+NK1.1+ T Cells for the Development of Small Intestinal Inflammation1
* Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, and Departments of
Anesthesiology, and
Nutrition and Physiological Chemistry, Osaka University Medical School, Osaka, Japan; and
Division of Mucosal Immunolgy, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan
To clarify the role of IL-15 at local sites, we engineered a
transgenic (Tg) mouse (T3b-IL-15 Tg) to overexpress
human IL-15 preferentially in intestinal epithelial cells by the use of
T3b-promoter. Although IL-15 was expressed in the entire
small intestine (SI) and large intestines of the Tg mice, localized
inflammation developed in the proximal SI only. Histopathologic study
revealed reduced villus length, marked infiltration of lymphocytes, and
vacuolar degeneration of the villus epithelium, beginning at 
3–4 mo
of age. The numbers of CD8+ T cells, especially
CD8
+ T cells expressing NK1.1, were dramatically
increased in the lamina propria of the involved SI. The severity of
inflammation corresponded to increased numbers of
CD8+NK1.1+ T cells and levels of
production of the Th1-type cytokines IFN-
and TNF-. Locally
overexpressed IL-15 was accompanied by increased resistance of
CD8+ NK1.1+ T cells to activation-induced
cell death. Our results suggest that chronic inflammation in the SI in
this murine model is mediated by dysregulation of epithelial
cell-derived IL-15. The model may contribute to understanding the role
of CD8+ T cells in human Crohn’s disease involving the
SI.
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