Published online
doi:10.1084/jem.20070618
The Journal of Experimental Medicine, Vol. 204, No. 7, 1665-1675
The Rockefeller University Press, 0022-1007 $30.00
© Wojciechowski et al.
Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis
Sara Wojciechowski1,
Pulak Tripathi1,
Tristan Bourdeau1,
Luis Acero2,
H. Leighton Grimes1,
Jonathan D. Katz2,
Fred D. Finkelman1,3, and
David A. Hildeman1
1 Division of Immunobiology and 2 Division of Endocrinology, Cincinnati Children's Hospital, Cincinnati, OH 45229
3 Division of Immunology, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229
CORRESPONDENCE David A. Hildeman: David.Hildeman{at}chmcc.org
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.
Abbreviations used: LCMV, lymphocytic choriomeningitis virus; pfu, plaque-forming unit; SP, single-positive thymocyte.
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