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

Summary 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.