Abstract
The gene for Wiskott-Aldrich syndrome (WAS) has been recently identified and cloned, but our knowledge of downstream events affected in WAS is limited to a few leucocyte cell surface molecules. To identify cell surface molecules whose abnormal expression could contribute to the functional impairment observed in WAS B and T lymphocytes, we studied the expression of a large panel of antigens on peripheral blood lymphoid cells (PBLC) and on isolated lymphocyte subpopulations from the spleen of WAS patients. WAS T lymphocytes from peripheral blood express increased levels of the activation antigens 4F2, CD49d, CD49e, CD53 and the activation/ memory marker CD45RO. In the spleen, however, WAS patients have more CD45RA CD4+ and CD8+ T lymphocytes than normal individuals, suggesting the selective accumulation of presumably naive cells in the WAS spleen. Interestingly, the naive phenotype of the lymphocytes that seem to accumulate in the WAS spleen is confirmed by the absence of increased expression of several activation antigens on their surface, and this correlated with their increased expression of CD43. These lymphocyte abnormalities were accompanied by an abnormal distribution of lymphocyte subsets within the spleen architecture, in particular by the lack of well developed germinal centres and T cell areas. We also found abnormal expression of CD43 and other sialylated proteins such as CDw75 and CD76, whose expression requires the action of specific sialyltransferases. This study shows that the combined impairment in cellular and humoral immunity observed in WAS is the result of multiple molecular abnormalities on the surface of WAS lymphocytes, that in turn might result in recirculation/migration anomalies.