Enforced expression of Bcl-2 partially restores cell numbers but not functions of TCRγδ intestinal intraepithelial T lymphocytes in IL-15-deficient mice

Kenji Nakazato, Hisakata Yamada, Toshiki Yajima, Yoshiko Kagimoto, Hiroyuki Kuwano, Yasunobu Yoshikai

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

IL-15 knockout (KO) mice have severely reduced numbers of TCRγδ 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 TCRγδ i-IEL, we introduced a bcl-2 transgene into EL-15 KO mice. In situ apoptosis of TCRγδ i-IEL was decreased in Bcl-2 transgenic (Tg) × IL-15 KO mice compared with EL-15 KO mice. The enforced expression of Bcl-2 partially restored the numbers of TCRγδ i-IEL in IL-15 KO mice. However, effector functions of TCRγδ i-IEL, including cytokine production and cytotoxic activity, were not recovered in Bcl-2 Tg × IL-15 KO mice. Importantly, TCRγδ i-IEL in Bcl-2 Tg × 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 TCRγδ 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 TCRγδ i-IEL and NK cells, but other signals from IL-15 are critical for inducing transcription factors, such as eomesodermin for their effector functions.

Original languageEnglish
Pages (from-to)757-764
Number of pages8
JournalJournal of Immunology
Volume178
Issue number2
DOIs
Publication statusPublished - Jan 15 2007

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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