Marrella, Veronica Poliani, Pietro L. Fontana, Elena Casati, Anna Maina, Virginia Cassani, Barbara Ficara, Francesca Cominelli, Manuela Schena, Francesca Paulis, Marianna Traggiai, Elisabetta Vezzoni, Paolo Grassi, Fabio Villa, Anna <jats:title>Abstract</jats:title> <jats:p>Omenn syndrome (OS) is an atypical primary immunodeficiency characterized by severe autoimmunity because of activated T cells infiltrating target organs. The impaired recombinase activity in OS severely affects expression of the pre-T-cell receptor complex in immature thymocytes, which is crucial for an efficient development of the thymic epithelial component. Anti-CD3ε monoclonal antibody (mAb) treatment in RAG2−/− mice was previously shown to mimic pre-TCR signaling promoting thymic expansion. Here we show the effect of anti-CD3ε mAb administration in the RAG2R229Q mouse model, which closely recapitulates human OS. These animals, in spite of the inability to induce the autoimmune regulator, displayed a significant amelioration in thymic epithelial compartment and an important reduction of peripheral T-cell activation and tissue infiltration. Furthermore, by injecting a high number of RAG2R229Q progenitors into RAG2−/− animals previously conditioned with anti-CD3ε mAb, we detected autoimmune regulator expression together with the absence of peripheral immunopathology. These observations indicate that improving epithelial thymic function might ameliorate the detrimental behavior of the cell-autonomous RAG defect. Our data provide important therapeutic proof of concept for future clinical applications of anti-CD3ε mAb treatment in severe combined immunodeficiency forms characterized by poor thymus function and autoimmunity.</jats:p> application/pdf https://sonar.ch/global/documents/139653 eng info:eu-repo/semantics/altIdentifier/doi/10.1182/blood-2012-01-406827 info:eu-repo/semantics/altIdentifier/issn/0006-4971 info:eu-repo/semantics/openAccess Blood. - American Society of Hematology. - 2012, vol. 120, no. 5, p. 1005-1014 Anti-CD3ε mAb improves thymic architecture and prevents autoimmune manifestations in a mouse model of Omenn syndrome: therapeutic implications http://purl.org/coar/resource_type/c_6501