Bim mediates apoptosis of CD127(lo) effector T cells and limits T cell memory

Eur J Immunol. 2006 Jul;36(7):1694-706. doi: 10.1002/eji.200635897.


Following an acute T cell response, most activated effector cells die, while some survive and become memory cells. The pro-apoptotic Bcl-2 family member, Bcl-2 interacting mediator of death (Bim) is critical for eliminating most effector T cells, while expression of CD127 (IL-7Ralpha) has been proposed to mark effector cells destined to become memory cells. Here, we examined the effects of Bim on the death of effector T cells in relationship to CD127 expression and on development of T cell memory following lymphocytic choriomeningitis virus (LCMV) infection. We found that large numbers of CD127(lo) LCMV-specific CD4(+) and CD8(+) T cells were lost in wild-type mice, but were spared in Bim(-/-) mice. Further, while the numbers of CD127(hi) T cells declined only slightly during contraction of the response in wild-type mice, they increased significantly in Bim(-/-) mice due to re-expression of CD127 on CD127(lo) T cells that had avoided apoptosis. Functional memory T cells were significantly increased in Bim(-/-) mice; however, they underwent a slow attrition due to decreased proliferative renewal. Taken together, these data suggest that the absence of Bim-mediated death of LCMV-specific CD4(+) and CD8(+) T cells in vivo can increase T cell memory, but other homeostatic mechanisms control the long-term maintenance of memory cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology*
  • Apoptosis Regulatory Proteins / deficiency
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / physiology*
  • Bcl-2-Like Protein 11
  • Cells, Cultured
  • Immunologic Memory*
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic choriomeningitis virus / immunology
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Proto-Oncogene Proteins / deficiency
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • Receptors, Interleukin-7 / metabolism*
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / virology


  • Apoptosis Regulatory Proteins
  • Bcl-2-Like Protein 11
  • Bcl2l11 protein, mouse
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Receptors, Interleukin-7