Restoration of thymopoiesis in pT alpha(-/-) mice by anti-CD3 epsilon antibody treatment or with transgenes encoding activated lck or tailless pT alpha

Mice deficient for the pre-TCR alpha (pT alpha) chain cannot form a pre-T cell receptor (TCR) and exhibit a severe defect in early T cell development, characterized by lack of ''beta selection'' and impaired generation of double-positive (DP) thymocytes. Here, we demonstrate that intraperitoneal injection of CD3 epsilon-specific antibodies into pT alpha(-/-) x RAG(-/-) mice or introduction of an activated p56(lck) transgene in pT alpha(-/-) mice fully restores the number of DP thymocytes, and that expression of a transgenic pT alpha chain lacking its cytoplasmic portion can overcome all developmental defects associated with pT alpha deficiency. These results allow a better definition of the role of pT alpha in pre-TCR signal transduction and provide conclusive evidence that the cytoplasmic tail of pT alpha is not essential for pre-TCR signaling.