Intrathymic Notch1 signaling directs T-lineage commitment and generation of CD4/CD8 double-positive (DP) thymocytes expressing αβ T cell receptors (TCRαβ). Notch signalling is dispensable for positive selection of classical T cells, but Notch functions during selection of innate T cells have not been studied. To determine how Notch signaling regulates development, polarization and homeostasis of innate T cells, we used CD4-Cre to generate mice that conditionally express activated Notch1 (and GFP) in DP thymocytes and their progeny. In 2 week-old neonates we also observed a 10-100 fold increase in numbers of unusual PLZF⁺ γδ thymocytes expressing CD4, Icos and Gata3. PLZF⁺ TCRαβ⁺ thymocytes were higher in frequency but not number.  However iNKT cells rarely expressed Vβ7 and were infrequent among this population, suggesting repertoire alterations. Furthermore, most Notch-induced PLZF⁺ αβ thymocytes expressed high levels of Gata3 and robustly produced IL-4, but not IFNγ or IL-17, demonstrating NKT2-like functional polarization. Interestingly, increased production of PLZF⁺ ɣδ and αβ thymocytes occurred only in neonates, during the time when these cells expand in normal mice. However, young adult mice had greatly increased numbers of γδ and/or αβ PLZF+ cells in spleen, suggesting abnormal post-thymic homeostasis. Mutant mice had dramatically shortened lifespans due to a multi-organ auto-inflammatory disease that was characterized by notable expansions of PLZF+ γδ or αβ T cells in spleen, liver and bone marrow but not lymph nodes. Preliminary data suggest that altered TCR signaling underlies some aspects of the Notch-induced phenotype. Thus, CD4-Cre-induced Notch1 activation causes dramatic over-production of IEL-like CD8αα and PLZF+ γδ or αβ T cells in the neonatal thymus, accompanied later by abnormal peripheral NKT cell homeostasis, excessive type 2 immunity and inflammation.