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PMID: 17591857 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis.

The Journal of experimental medicine ·Vol. 204 ·No. 7 ·2007-07-09 ·Pages 1665-75

Wojciechowski S, Tripathi P, Bourdeau T, Acero L, Grimes HL, Katz JD, Finkelman FD, Hildeman DA

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.

MeSH Terms
Animals Apoptosis Regulatory Proteins/deficiency,genetics,physiology Bcl-2-Like Protein 11 Bone Marrow/immunology,physiology Homeostasis Immunologic Memory/physiology Interleukin-7/deficiency Lymphocyte Activation Lymphocytic Choriomeningitis/immunology Membrane Proteins/deficiency,genetics,physiology Mice Mice, Knockout Proto-Oncogene Proteins/deficiency,genetics,physiology Proto-Oncogene Proteins c-bcl-2/deficiency,genetics,physiology T-Lymphocytes/immunology,physiology Thymectomy
Chemicals
Apoptosis Regulatory Proteins Bcl-2-Like Protein 11 Bcl2l11 protein, mouse Interleukin-7 Membrane Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Wojciechowski Sara
Division of Immunobiology, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA.
Tripathi Pulak
Bourdeau Tristan
Acero Luis
Grimes H Leighton
Katz Jonathan D
Finkelman Fred D
Hildeman David A
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20070618
Published
2007-07-09
Epub
2007-00-25
Pages
1665-75
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2118628
Subset
IM
Grants
NCI NIH HHS · CA 105152 · United States
NIAID NIH HHS · R01 AI057753 · United States
NIAID NIH HHS · R01 AI055848 · United States
NIAID NIH HHS · AI 558848 · United States
NIAID NIH HHS · AI 057753 · United States
NCI NIH HHS · R01 CA105152 · United States
NIAID NIH HHS · R56 AI057753 · United States
External Links
PubMed source DOI: 10.1084/jem.20070618 PMC Full Text View journal details
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