Demonstration of abnormalities in expression of thymic epithelial surface antigens in severe cellular immunodeficiency diseases.

Thymic epithelium from three patients with severe cellular immunodeficiency diseases were compared with age-matched normal thymic epithelium using three markers of human thymic epithelium and antibodies against thymosin alpha 1, thymopoietin, and thymosin beta 4. We have previously shown that normal thymic epithelium reacts with antibodies against GQ gangliosides (antibody A2B5) and binds tetanus toxin (TT). In addition, some areas of normal thymic epithelium express human Thy-1 antigen. We found thymic epithelium in patients with severe cellular immunodeficiency diseases to be different from normal subjects. Two children with severe combined immunodeficiency disease (SCID) had thymic epithelium that bound anti-GQ ganglioside antibody but, unlike in normals, did not bind TT. The patient with severe cellular immunodeficiency and normal serum immunoglobulins (Nezelof syndrome) had thymic epithelium that bound TT but, unlike normal thymic epithelium, did not react with anti-GQ ganglioside antibody. Thymic epithelium from both SCID and Nezelof syndrome patients contained thymosin alpha 1, thymopoietin, and thymosin beta 4 and expressed human Thy-1 antigen. In contrast to SCID thymus rudiments, Nezelof thymus contained numerous (though fewer than normal) lymphocytes with mature T cell surface antigens. Thus, using these probes of human thymic epithelium, we have demonstrated heterogeneous defects in thymic epithelial surface marker expression in severe primary cellular immunodeficiency diseases. These defects presumably reflect abnormalities of in vivo thymic epithelial maturation.