Enforced expression of Bcl-2 partially restores cell numbers but not functions of TCRgammadelta intestinal intraepithelial T lymphocytes in IL-15-deficient mice.
IL-15 knockout (KO) mice have severely reduced numbers of TCRgammadelta intestinal intraepithelial T lymphocytes (i-IEL), suggesting requirements of IL-15 signaling in the development or maintenance of i-IEL. To determine an involvement of survival signals via Bcl-2 in IL-15-mediated homeostasis of TCRgammadelta i-IEL, we introduced a bcl-2 transgene into IL-15 KO mice. In situ apoptosis of TCRgammadelta i-IEL was decreased in Bcl-2 transgenic (Tg) x IL-15 KO mice compared with IL-15 KO mice. The enforced expression of Bcl-2 partially restored the numbers of TCRgammadelta i-IEL in IL-15 KO mice. However, effector functions of TCRgammadelta i-IEL, including cytokine production and cytotoxic activity, were not recovered in Bcl-2 Tg x IL-15 KO mice. Importantly, TCRgammadelta i-IEL in Bcl-2 Tg x IL-15 KO mice expressed a reduced level of eomesodermin, a transcription factor critical for effector functions of NK cells and CD8(+) T cells. Similar to the case of TCRgammadelta i-IEL, enforced expression of Bcl-2 restored the numbers but not the functions of NK cells in IL-15 KO mice. These results suggest that Bcl-2-mediated survival signal is involved in the IL-15-mediated homeostasis of TCRgammadelta i-IEL and NK cells, but other signals from IL-15 are critical for inducing transcription factors, such as eomesodermin for their effector functions.
Nakazato
Kenji
K
Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Yamada
Hisakata
H
Yajima
Toshiki
T
Kagimoto
Yoshiko
Y
Kuwano
Hiroyuki
H
Yoshikai
Yasunobu
Y
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D019409:Interleukin-15 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*
C491198:Eomes protein, mouse; D019409:Interleukin-15; D019253:Proto-Oncogene Proteins c-bcl-2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D020825:T-Box Domain Proteins