Bim mediates the elimination of functionally unfit Th1 responders from the memory pool

PLoS One. 2013 Jun 28;8(6):e67363. doi: 10.1371/journal.pone.0067363. Print 2013.

Abstract

Selective clonal deletion in the CD4(+) T cell compartment during the transition from effector to memory is accompanied by enhanced expression of the pro-apoptotic Bcl-2 family member Bim. Here, we show that Bim deficiency enables the survival of poorly functional Th1 responders that are normally eliminated during contraction. However, rescued bim(-/-) CD4(+) "memory" T cells continued to demonstrate deficient effector functions, poor sensitivity to antigen and an inability to respond to secondary challenge. Our results demonstrate that Bim activity plays a key role in shaping the CD4(+) memory T cell repertoire, ensuring the emergence of highly functional CD4(+) memory T cells and the elimination of Th1 effector cells with sub-optimal function. We propose that Bim is a key mediator of T cell death in the absence of appropriate TCR-driven activation and differentiation.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Apoptosis Regulatory Proteins / physiology
  • Bcl-2-Like Protein 11
  • Gene Expression
  • Immunologic Memory*
  • Listeriosis / immunology
  • Listeriosis / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Membrane Proteins / physiology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins / physiology
  • Th1 Cells / immunology*
  • Th1 Cells / microbiology
  • Transcriptional Activation
  • Up-Regulation

Substances

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