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

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