| First Author | Marrella V | Year | 2012 |
| Journal | Blood | Volume | 120 |
| Issue | 5 | Pages | 1005-14 |
| PubMed ID | 22723555 | Mgi Jnum | J:189196 |
| Mgi Id | MGI:5444594 | Doi | 10.1182/blood-2012-01-406827 |
| Citation | Marrella V, et al. (2012) Anti-CD3epsilon mAb improves thymic architecture and prevents autoimmune manifestations in a mouse model of Omenn syndrome: therapeutic implications. Blood 120(5):1005-14 |
| abstractText | 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-CD3epsilon 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-CD3epsilon mAb administration in the RAG2(R229Q) 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 RAG2(R229Q) progenitors into RAG2(-/-) animals previously conditioned with anti-CD3epsilon 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-CD3epsilon mAb treatment in severe combined immunodeficiency forms characterized by poor thymus function and autoimmunity. |
