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.
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.
Lai
Yein-Gei
YG
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei. Taiwan.
Hou
Mau-Sheng
MS
Hsu
Yaw-Wen
YW
Chang
Chin-Ling
CL
Liou
Yae-Huei
YH
Tsai
Ming-Han
MH
Lee
Fan
F
Liao
Nan-Shih
NS
D000818:Animals; D016827:CD8 Antigens / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000276:immunology*; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006706:Homeostasis / Q000276:immunology*; D019409:Interleukin-15 / Q000502:physiology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D008822:Mice, Transgenic; D013234:Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D019409:Interleukin-15