Transgenic Bcl-3 slows T cell proliferation

Int Immunol. 2009 Apr;21(4):339-48. doi: 10.1093/intimm/dxp002. Epub 2009 Feb 10.

Abstract

Immunological adjuvants, such as bacterial LPS, increase the mRNA levels of the IkB-related NF-kappaB transcriptional transactivator, Bcl-3, in activated T cells. Adjuvants also increase the life expectancy of activated T cells, as does over-expression of Bcl-3, suggesting that Bcl-3 is part of the pathway whereby adjuvants affect T cell lifespans. However, previous reports, confirmed here, show that adjuvants also increase the life expectancies of Bcl-3-deficient T cells, making Bcl-3's role and effects in adjuvant-induced survival uncertain. To investigate the functions of Bcl-3 further, here we confirm the adjuvant-induced expression of Bcl-3 mRNA and show Bcl-3 induction at the protein level. Bcl-3 was expressed in mice via a transgene driven by the human CD2 promoter. Like other protective events, over-expression of Bcl-3 slows T cell activation very early in T cell responses to antigen, both in vitro and in vivo. This property was intrinsic to the T cells over-expressing the Bcl-3 and did not require Bcl-3 expression by other cells such as antigen-presenting cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • B-Cell Lymphoma 3 Protein
  • Cell Proliferation
  • Cell Survival / physiology
  • Cells, Cultured
  • Lymphocyte Activation* / drug effects
  • Lymphocyte Activation* / genetics
  • Mice
  • Mice, Transgenic
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins / genetics
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics

Substances

  • Adjuvants, Immunologic
  • B-Cell Lymphoma 3 Protein
  • BCL3 protein, human
  • Bcl3 protein, mouse
  • Proto-Oncogene Proteins
  • Transcription Factors