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

J Immunol. 2007 Jan 15;178(2):757-64. doi: 10.4049/jimmunol.178.2.757.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Proliferation
  • Cells, Cultured
  • Epithelial Cells / metabolism*
  • Gene Expression
  • Humans
  • Interleukin-15 / deficiency
  • Interleukin-15 / genetics
  • Interleukin-15 / metabolism*
  • Intestinal Mucosa / metabolism*
  • Intestines / cytology
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • T-Box Domain Proteins / metabolism
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / metabolism*

Substances

  • Eomes protein, mouse
  • Interleukin-15
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Antigen, T-Cell, gamma-delta
  • T-Box Domain Proteins