| First Author | Pellegrini M | Year | 2004 |
| Journal | J Exp Med | Volume | 200 |
| Issue | 9 | Pages | 1189-95 |
| PubMed ID | 15504823 | Mgi Jnum | J:94907 |
| Mgi Id | MGI:3522070 | Doi | 10.1084/jem.20041328 |
| Citation | Pellegrini M, et al. (2004) Loss of Bim increases T cell production and function in interleukin 7 receptor-deficient mice. J Exp Med 200(9):1189-95 |
| abstractText | 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-7Ralpha 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 mice, indicating that activation of a proapoptotic Bcl-2 family member causes death of immature 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-/- 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 might be useful for boosting immune responses in immunodeficient patients. |
