Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis
Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis
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.
- Cincinnati Children's Hospital Medical Center United States
- University System of Ohio United States
- University of Cincinnati United States
- University of Cincinnati Medical Center United States
Mice, Knockout, Bcl-2-Like Protein 11, Interleukin-7, T-Lymphocytes, Membrane Proteins, Articles, Lymphocytic Choriomeningitis, Lymphocyte Activation, Thymectomy, Mice, Proto-Oncogene Proteins c-bcl-2, Bone Marrow, Proto-Oncogene Proteins, Animals, Homeostasis, Apoptosis Regulatory Proteins, Immunologic Memory
Mice, Knockout, Bcl-2-Like Protein 11, Interleukin-7, T-Lymphocytes, Membrane Proteins, Articles, Lymphocytic Choriomeningitis, Lymphocyte Activation, Thymectomy, Mice, Proto-Oncogene Proteins c-bcl-2, Bone Marrow, Proto-Oncogene Proteins, Animals, Homeostasis, Apoptosis Regulatory Proteins, Immunologic Memory
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