NF-κB is required for the positive selection of CD8+ thymocytes

To examine the role of NF-kappaB in T cell development, we analyzed thymocyte ontogeny in transgenic (mutant I-kappaB alpha (mI-kappaB alpha)) mice that express a superinhibitory form of the NF-kappaB inhibitory protein, I-kappaB alpha (I-kappaB alpha (A32/36)), under the control of the T cell-specific CD2 promoter and enhancer. Thyme from mI-kappaB alpha 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-kappaB alpha mice, To test directly whether NF-kappaB was required for positive or negative selection, we generated mI-kappaB alpha mice expressing the H-Y or 2C alpha beta TCR transgenes. Expression of the I-kappaB alpha (A32/36) 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-kappaB alpha (A32/36) transgene, Taken together, these results identified a NF-kappaB-dependent transcriptional pathway that is selectively required for the positive selection of CD8(+) thymocytes.