iPSC-Based Modeling of RAG2 Severe Combined Immunodeficiency Reveals Multiple T Cell Developmental Arrests
Maria Themeli, Amiet Chhatta, Hester Boersma, Henk Jan Prins, Martijn Cordes, Edwin de Wilt, Aïda Shahrabi Farahani, Bart Vandekerckhove, Mirjam van der Burg, Rob C. Hoeben, Frank J. T. Staal, Harald Mikkers
Abstract
natural killer (NK) cell-like cells. T cell receptor D rearrangements were completely absent in RAG2SCID cells, whereas the rare T cell receptor B rearrangements were likely the result of illegitimate rearrangements. Repair of RAG2 restored the capacity to induce T cell receptor rearrangements, normalized T cell development, and corrected the NK cell-like phenotype. In conclusion, we succeeded in generating an iPSC-based RAG2-SCID model, which enabled the identification of previously unrecognized disorder-related T cell developmental roadblocks.