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PMID:17591857

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Citation

Wojciechowski, S, Tripathi, P, Bourdeau, T, Acero, L, Grimes, HL, Katz, JD, Finkelman, FD and Hildeman, DA (2007) Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis. J. Exp. Med. 204:1665-75

Abstract

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.

Links

PubMed PMC2118628 Online version:10.1084/jem.20070618

Keywords

Animals; Apoptosis Regulatory Proteins/deficiency; Apoptosis Regulatory Proteins/genetics; Apoptosis Regulatory Proteins/physiology; Bone Marrow/immunology; Bone Marrow/physiology; Homeostasis; Immunologic Memory/physiology; Interleukin-7/deficiency; Lymphocyte Activation; Lymphocytic Choriomeningitis/immunology; Membrane Proteins/deficiency; Membrane Proteins/genetics; Membrane Proteins/physiology; Mice; Mice, Knockout; Proto-Oncogene Proteins/deficiency; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/physiology; Proto-Oncogene Proteins c-bcl-2/deficiency; Proto-Oncogene Proteins c-bcl-2/genetics; Proto-Oncogene Proteins c-bcl-2/physiology; T-Lymphocytes/immunology; T-Lymphocytes/physiology; Thymectomy

Significance

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References

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