NF-kappa B is required for the positive selection of CD8(+) thymocytes

To examine the role of NF-kappaB in T cell development, we analyzed thymocy te ontogeny in transgenic (mutant I-kappaB alpha (mI-kappaB alpha)) mice th at express a superinhibitory form of the NF-kappaB inhibitory protein, I-ka ppaB alpha (I-kappaB alpha (A32/36)), under the control of the T cell-speci fic CD2 promoter and enhancer. Thyme from mI-kappaB alpha mice contained in creased 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 selectio n, was decreased on DP thymocytes from the mI-kappaB alpha mice, To test di rectly whether NF-kappaB was required for positive or negative selection, w e generated mI-kappaB alpha mice expressing the H-Y or 2C alpha beta TCR tr ansgenes. Expression of the I-kappaB alpha (A32/36) transgene caused a bloc k 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, the se results identified a NF-kappaB-dependent transcriptional pathway that is selectively required for the positive selection of CD8(+) thymocytes.