Abnormal T lymphocyte development induced by targeted overexpression of IκBα

A role in thymic maturation for factors of the NF-κB family has long been suspected, but not yet proven. Transgenic mice with a lymphocyte-specific defect in NF-κB activation were produced by targeted expression of human IκBα. The thymic cellularity of these mice was significantly decreased. The proportion of mature, TCR^high thymocytes of the αβ lineage was reduced, and the remaining TCR^high population contained an unusually high proportion of double-positive cells. This defect in maturation resulted in a transgene dose-dependent reduction in peripheral T lymphocytes, with the CD8 lineage being more severely affected. These data provide direct evidence for the involvement of NF-κB/Rel family proteins in late stages of T lymphocyte development, coincident with positive and negative selection.