Differential Role of the Transcription Factor NF-κB in Selection and Survival of CD4+ and CD8+ Thymocytes

Eijiro Jimi, Ian Strickland, Reinhard E. Voll, Meixiao Long, Sankar Ghosh

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Inhibition of the transcription factor nuclear factor (NF)-κB activity leads to a reduction in numbers of CD8+ single-positive (SP) thymocytes, suggesting a selective role for NF-κB in these cells. To further explore the role of NF-κB in SP thymocytes, we utilized transgenic models that allowed either inhibition or activation of NF-κB. We showed that activation of NF-κB played an important role in the selection of major histocompatibility complex (MHC) class I-restricted CD8+ T cells. Surprisingly, NF-κB was not activated in positively selected CD4+ thymocytes, and inhibition of NF-κB did not perturb positive or negative selection of CD4+ cells. However, enforced activation of NF-κB via a constitutively active inhibitor of κB (IκB) kinase transgene led to a nearly complete deletion of CD4 cells by pushing positively selecting CD4+ cells into negative selection. These studies therefore revealed a surprising difference of NF-κB activation in CD4+ and CD8+ thymocytes and suggested that NF-κB contributes to the establishment of thresholds of signaling that determine positive or negative selection of thymocytes.

Original languageEnglish
Pages (from-to)523-537
Number of pages15
JournalImmunity
Volume29
Issue number4
DOIs
Publication statusPublished - Oct 17 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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