Restoration of thymopoiesis in pT alpha-/- mice by anti-CD3epsilon 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 CD3epsilon-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.