Anti-CD3ε mAb improves thymic architecture and prevents autoimmune manifestations in a mouse model of Omenn syndrome: therapeutic implications.

[omenn syndrome]

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-CD 3 ε monoclonal antibody (mAb ) treatment in RAG 2 (-/-) mice was previously shown to mimic pre-TCR signaling promoting thymic expansion . Here we show the effect of anti-CD 3 ε mAb administration in the RAG 2 (R 229 Q ) 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 RAG 2 (R 229 Q ) progenitors into RAG 2 (-/-) animals previously conditioned with anti-CD 3 ε 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-CD 3 ε mAb treatment in severe combined immunodeficiency forms characterized by poor thymus function and autoimmunity .

Diseases
Validation

Diseases presenting "immunodeficiency" symptom

adrenal incidentaloma

allergic bronchopulmonary aspergillosis

cushing syndrome

dracunculiasis

hirschsprung disease

hodgkin lymphoma, classical

homocystinuria without methylmalonic aciduria

kabuki syndrome

legionellosis

malignant atrophic papulosis

oculocutaneous albinism

omenn syndrome

papillon-lefèvre syndrome

primary effusion lymphoma

primary hyperoxaluria type 1

pyomyositis

severe combined immunodeficiency

sneddon syndrome

werner syndrome

wiskott-aldrich syndrome

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

This symptom has already been validated