NF-κB Is Required for the Positive Selection of CD8+ Thymocytes

To examine the role of NF-κB in T cell development, we analyzed thymocyte ontogeny in transgenic (mutant I-κBα (mI-κBα)) mice that express a superinhibitory form of the NF-κB inhibitory protein, I-κBα (I-κBαA32/36), under the control of the T cell-specific CD2 promoter and enhancer. Thymi from mI-κBα mice contained increased numbers of double-positive (DP) and decreased numbers of both CD4+ and CD8+ single-positive cells, consistent with a block in DP thymocyte maturation. In addition, expression of CD69, a marker of positive selection, was decreased on DP thymocytes from the mI-κBα mice. To test directly whether NF-κB was required for positive or negative selection, we generated mI-κBα mice expressing the H-Y or 2C αβ TCR transgenes. Expression of the I-κBαA32/36 transgene caused a block in the positive selection of CD8+ single-positive cells in both strains of TCR transgenic animals. In contrast, negative selection was unaffected by expression of the I-κBαA32/36 transgene. Taken together, these results identified a NF-κB-dependent transcriptional pathway that is selectively required for the positive selection of CD8+ thymocytes.