IL-15 does not affect IEL development in the thymus but regulates homeostasis of putative precursors and mature CD8 alpha alpha+ IELs in the intestine

• Published in: The Journal of immunology (1950) Vol. 180; no. 6; pp. 3757 - 3765
• Main Authors: Lai, Yein-Gei, Hou, Mau-Sheng, Hsu, Yaw-Wen, Chang, Chin-Ling, Liou, Yae-Huei, Tsai, Ming-Han, Lee, Fan, Liao, Nan-Shih
• Format: Journal Article
• Language: English
• Published: United States 15.03.2008
• Subjects: Animals; CD8 Antigens - biosynthesis; Cell Differentiation - immunology; Cell Survival - genetics; Cell Survival - immunology; Cells, Cultured; Epithelial Cells - cytology; Epithelial Cells - immunology; Epithelial Cells - metabolism; Homeostasis - immunology; Interleukin-15 - physiology; Intestinal Mucosa - cytology; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Lymphocyte Subsets - cytology; Lymphocyte Subsets - immunology; Lymphocyte Subsets - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Nude; Mice, Transgenic; Stem Cells - cytology; Stem Cells - immunology; Stem Cells - metabolism; Thymus Gland - cytology; Thymus Gland - immunology; Thymus Gland - metabolism
• ISSN: 0022-1767
• DOI: 10.4049/jimmunol.180.6.3757

Mice devoid of the IL-15 system lose over 90% of CD8alphaalpha(+) TCRalphabeta and TCRgammadelta intestinal intraepithelial lymphocytes (iIELs). Previous work revealed that IL-15Ralpha and IL-15 expressed by parenchymal cells, but not by bone marrow-derived cells, are required for normal CD8alphaalpha(+) iIEL homeostasis. However, it remains unclear when and how the IL-15 system affects CD8alphaalpha(+) iIELs through their development. This study found that IL-15Ralpha is dispensable for the thymic stage of CD8alphaalpha(+) TCRalphabeta and TCRgammadelta iIEL development but is required for the maintenance and/or differentiation of the putative lineage marker negative precursors in the intestinal epithelium, especially for the most mature CD8 single positive subset. Moreover, the IL-15 system directly supports the survival of mature CD8alphaalpha(+) iIEL in vivo. Taken together, this study suggests that regulation of CD8alphaalpha(+) iIEL homeostasis by the IL-15 system does not occur in the thymus but involves mature cells and putative precursors in the intestine.