IL-15-dependent activation-induced cell death-resistant Th1 type CD8 alpha beta+NK1.1+ T cells for the development of small intestinal inflammation.

Abstract

To clarify the role of IL-15 at local sites, we engineered a transgenic (Tg) mouse (T3(b)-IL-15 Tg) to overexpress human IL-15 preferentially in intestinal epithelial cells by the use of T3(b)-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 approximately 3-4 mo of age. The numbers of CD8(+) T cells, especially CD8alphabeta(+) 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 CD8alphabeta(+)NK1.1(+) T cells and levels of production of the Th1-type cytokines IFN-gamma and TNF-alpha. Locally overexpressed IL-15 was accompanied by increased resistance of CD8alphabeta(+) 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.

• Authors: Noriyuki Ohta, Takachika Hiroi, Mi-Na Kweon, Naotoshi Kinoshita, Myoung Ho Jang, Tadashi Mashimo, Jun-Ichi Miyazaki, Hiroshi Kiyono
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 169 Issue 1 Pg. 460-8 (Jul 01 2002) ISSN: 0022-1767 [Print] United States
• PMID: 12077277 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens
• Antigens, Ly
• Antigens, Surface
• CD8 Antigens
• CD8alphabeta antigen
• Cytokines
• Interleukin-15
• KLRB1 protein, human
• Klrb1c protein, mouse
• Lectins, C-Type
• NK Cell Lectin-Like Receptor Subfamily B
• Proteins
• Receptors, Antigen, T-Cell, alpha-beta

Topics

• Animals
• Antigens (biosynthesis)
• Antigens, Ly
• Antigens, Surface
• CD8 Antigens (biosynthesis)
• Cell Death (immunology)
• Cell Movement (genetics, immunology)
• Cytokines (biosynthesis)
• Humans
• Immunity, Innate (genetics)
• Immunologic Memory (genetics)
• Inflammation (immunology, pathology)
• Interleukin-15 (biosynthesis, genetics, physiology)
• Intestinal Mucosa (metabolism, pathology)
• Intestine, Small (immunology, pathology)
• Killer Cells, Natural (immunology, metabolism)
• Lectins, C-Type
• Lymph Nodes (immunology, pathology)
• Lymphocyte Activation (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred ICR
• Mice, Transgenic
• NK Cell Lectin-Like Receptor Subfamily B
• Protein Biosynthesis
• Proteins
• Receptors, Antigen, T-Cell, alpha-beta (biosynthesis)
• T-Lymphocyte Subsets (immunology, metabolism, pathology)
• Th1 Cells (immunology, metabolism)