ABNORMAL T-LYMPHOCYTE DEVELOPMENT INDUCED BY TARGETED OVEREXPRESSION OF I-KAPPA-B-ALPHA

A role in thymic maturation for factors of the NF-kappa B family has l ong been suspected, but not yet proven, Transgenic mice with a lymphoc yte-specific defect in NF-kappa B activation were produced by targeted expression of human I kappa B alpha, The thymic cellularity of these mice was significantly decreased, The proportion of mature, TCRhigh th ymocytes of the cup lineage was reduced, and the remaining TCRhigh pop ulation contained an unusually high proportion of double-positive cell s, This defect in maturation resulted in a transgene dose-dependent re duction in peripheral T lymphocytes, with the CD8 lineage being more s everely affected, These data provide direct evidence for the involveme nt of NF-kappa B/Rel family proteins in late stages of T lymphocyte de velopment, coincident with positive and negative selection.