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IL-15 Does Not Affect IEL Development in the Thymus but Regulates Homeostasis of Putative Precursors and Mature CD8⁺ IELs in the Intestine¹

Yein-Gei Lai^*,, Mau-Sheng Hou, Yaw-Wen Hsu, Chin-Ling Chang^*,, Yae-Huei Liou, Ming-Han Tsai, Fan Lee and Nan-Shih Liao^2,*,

^* Graduate Institute of Life Sciences, National Defense Medical Center, Institute of Molecular Biology, Academia Sinica, Taipei, and Division of Nephrology, Chang Gung Memorial Hospital, Taoyuan, Taiwan

Mice devoid of the IL-15 system lose over 90% of CD8⁺ TCRβ and TCR intestinal intraepithelial lymphocytes (iIELs). Previous work revealed that IL-15R and IL-15 expressed by parenchymal cells, but not by bone marrow-derived cells, are required for normal CD8⁺ iIEL homeostasis. However, it remains unclear when and how the IL-15 system affects CD8⁺ iIELs through their development. This study found that IL-15R is dispensable for the thymic stage of CD8⁺ TCRβ and TCR 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 CD8⁺ iIEL in vivo. Taken together, this study suggests that regulation of CD8⁺ iIEL homeostasis by the IL-15 system does not occur in the thymus but involves mature cells and putative precursors in the intestine.

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¹ This work was supported by Taiwanese National Science Council Grant 95-2320-B-001-033 (to Y.-G.L. and Y.-H.L.). M.-S.H. and Y.-W.H. were supported by Academia Sinica.

² Address correspondence and reprint requests to Dr. Nan-Shih Liao, Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan. E-mail address: mbfelix{at}imb.sinica.edu.tw

³ Abbreviations used in this paper: IEL, intraepithelial lymphocyte; iIEL, intestinal IEL; BM, bone marrow; ATXBM, adult mice thymectomized and bone marrow re-constituted; PP, Peyer’s patches; PI, propidium iodide; lin ^–, lineage marker negative; CP, cryptopatch; SP, single positive; DP, double positive; TN, triple negative; SA, streptavidin; PB, Pacific blue; B6, C57BL/6J; β, TCRβ⁺; , TCR⁺; eGFP, enriched GFP; WT, wild type.