Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis
| Autor: | Fred D. Finkelman, Pulak Tripathi, Luis Acero, Tristan Bourdeau, H. Leighton Grimes, Jonathan D. Katz, Sara Wojciechowski, David A. Hildeman |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
T-Lymphocytes
cells Immunology Lymphocytic Choriomeningitis Biology Lymphocyte Activation Lymphocytic choriomeningitis Article Mice 03 medical and health sciences 0302 clinical medicine Bone Marrow In vivo Proto-Oncogene Proteins hemic and lymphatic diseases medicine Animals Homeostasis Immunology and Allergy neoplasms 030304 developmental biology Mice Knockout 0303 health sciences Bcl-2-Like Protein 11 Interleukin-7 Membrane Proteins hemic and immune systems Articles Thymectomy medicine.disease In vitro Cell biology medicine.anatomical_structure Proto-Oncogene Proteins c-bcl-2 Bone marrow biological phenomena cell phenomena and immunity Apoptosis Regulatory Proteins Immunologic Memory Memory T cell CD8 Ex vivo 030215 immunology |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | We examined the role of the antiapoptotic molecule Bcl-2 in combating the proapoptotic molecule Bim in control of naive and memory T cell homeostasis using Bcl-2(-/-) mice that were additionally deficient in one or both alleles of Bim. Naive T cells were significantly decreased in Bim(+/-)Bcl-2(-/-) mice, but were largely restored in Bim(-/-)Bcl-2(-/-) mice. Similarly, a synthetic Bcl-2 inhibitor killed wild-type, but not Bim(-/-), T cells. Further, T cells from Bim(+/-)Bcl-2(-/-) mice died rapidly ex vivo and were refractory to cytokine-driven survival in vitro. In vivo, naive CD8(+) T cells required Bcl-2 to combat Bim to maintain peripheral survival, whereas naive CD4(+) T cells did not. In contrast, Bim(+/-)Bcl-2(-/-) mice generated relatively normal numbers of memory T cells after lymphocytic choriomeningitis virus infection. Accumulation of memory T cells in Bim(+/-)Bcl-2(-/-) mice was likely caused by their increased proliferative renewal because of the lymphopenic environment of the mice. Collectively, these data demonstrate a critical role for a balance between Bim and Bcl-2 in controlling homeostasis of naive and memory T cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|