NF-kB Is Required for the Positive Selection of CD8 Thymocytes

To examine the role of NF-kB in T cell development, we analyzed thymocyte ontogeny in transgenic (mutant I-kBa (mI-kBa)) mice that express a superinhibitory form of the NF-kB inhibitory protein, I-kBa (I-kBaA32/36), under the control of the T cell-specific CD2 promoter and enhancer. Thymi from mI-kBa 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-kBa mice. To test directly whether NF-kB was required for positive or negative selection, we generated mI-kBa mice expressing the H-Y or 2C ab TCR transgenes. Expression of the I-kBaA32/36 transgene caused a block in the positive selection of CD8 1 single-positive cells in both strains of TCR transgenic animals. In contrast, negative selection was unaffected by expression of the I-kBaA32/36 transgene. Taken together, these results identified a NF-kB-dependent transcriptional pathway that is selectively required for the positive selection of CD8 thymocytes. The Journal of Immunology, 2000, 165: 5004–5010.