Loss of Bim increases T cell production and function in interleukin 7 receptor-deficient mice
- Author(s)
- Pellegrini, M; Bouillet, P; Robati, M; Belz, GT; Davey, GM; Strasser, A;
- Details
- Publication Year 2004-11-01,Volume 200,Issue #9,Page 1189-1195
- Journal Title
- JOURNAL OF EXPERIMENTAL MEDICINE
- Publication Type
- Journal Article
- Abstract
- Interleukin (IL)-7 receptor (R) signaling is essential for T and B lymphopoiesis by promoting proliferation, differentiation, and survival of cells. Mice lacking either IL-7 or the IL-71Ralpha chain have abnormally low numbers of immature as well as mature T and B lymphocytes. Transgenic expression of the apoptosis inhibitor Bcl-2 rescues T cell development and function in IL-7Ralpha-deficient trice, indicating that activation of a proapoptotic Bcl-2 fancily member causes death of miniature and mature T cells. BH3-only proteins such as Bim, which are distant proapoptotic members of the Bcl-2 family, are essential initiators of programmed cell death and stress-induced apoptosis. We generated Bim/IL-7Ralpha double deficient mice and found that loss of Bim significantly increased thymocyte numbers, restored near normal numbers of mature T cells in the blood and spleen, and enhanced cytotoxic T cell responses to virus infection in IL-7Ralpha(-l-) mice. These results indicate that Bim cooperates with other proapoptotic proteins in the death of IL-7-deprived T cell progenitors in vivo, but is the major inducer of this pathway to apoptosis in mature T cells. This indicates that pharmacological inhibition of Bim function night be useful for boosting immune responses in immunodeficient patients.
- Publisher
- ROCKEFELLER UNIV PRESS
- Keywords
- FAMILY-MEMBER BIM; B-CELLS; GAMMA-CHAIN; PROTEIN BIM; BCL-2; IL-7; LYMPHOPOIESIS; APOPTOSIS; BAX; HOMEOSTASIS
- Publisher's Version
- https://doi.org/10.1084/jem.20041328
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2004-11-01 12:00:00