ABNORMAL IN-VITRO THYMOCYTE DIFFERENTIATION IN A PATIENT WITH SEVERE COMBINED IMMUNODEFICIENCY NEZELOFS SYNDROME

An in vitro coculture model system of CD34+ stem cells and allogenic c ultured thymic epithelia fragments was used to evaluate thymocyte diff erentiation in a 9-month-old child of Amish descent with Nezelof syndr ome. Though the patient's stem cells differentiate to acquire normal e xpression of CD2 and CD7, later steps of maturation were abnormal. The re was detectable but reduced expression of CD3 and CD4 phenotypes. CD 44+ expression, however, was markedly reduced. CD44 is an adhesion mol ecule, interacting with the matrix ligands hyaluronan and fibronectin, and is expressed early in thymocyte differentiation and subsequently in mature T cells. It is hypothesized that abnormal expression of CD44 in a variant of severe combined immunodeficiency, Nezelof's syndrome, interferes with normal thymocyte and thymic epithelial interaction, w hich leads to abnormal thymocyte differentiation.