Overexpression of LFA-1 and ICAM-1 in Down syndrome thymus. Implications for abnormal thymocyte maturation

The interaction between lymphocyte function-associated antigen 1 (LFA-1) on thymocytes and intercellular adhesion molecule 1 (ICAM-1) on the thymic stroma plays an important role in thymocyte maturation. Consequently, we examined the constitutive expression of LFA-1 and ICAM-1 in postnatal human thymus from children with Down syndrome (trisomy 21, DS) and age-matched control children. We studied DS thymuses because this aneuploid condition is associated with abnormal thymic anatomy and patterns of thymocyte maturation and the affected individuals have a greatly increased incidence of infection. In addition, the beta -chain for LFA-1 is encoded on human chromosome 21, suggesting that trisomy 21 thymocytes may overexpress this addesion molecule. Using immunofluorescence and flow cytometry, LFA-1 beta expression was evaluated in eleven pairs of DS and age-matched control thymocytes. Our findings support a role for cytokines in the regulation of adhesion molecule expression in the thymus and suggest that the increased expression and abnormal distribution of adhesion molecules in DS thymuses alters the interaction between developing thymocytes and the thymic stroma and results in the abnormal thymocyte maturation observed in DS.