Defective depletion of CD45-null thymocytes by the Staphylococcus aureus Enterotoxin B superantigen

Abstract

The development of a normal T-cell repertoire is critically dependent on the negative and positive selection events which occur at the CD4 +CD8 + (double positive, DP) stage of thymic development. Depending on the avidity of the T-cell antigen receptor (TCR) for peptides presented within the thymus, DP thymocytes are either positively selected for maturation to CD4 +CD8 + single positive cells or are depleted by apoptosis. The addition of superantigen to thymocytes within foetal thymic organ culture (FTOC) mimics the negative selection signal of potentially autoreactive thymocytes and induces the responding population of thymocytes to apoptose. Here we present evidence that the transmembrane phosphotyrosine phosphatase CD45 critically regulates TCR-induced signals in thymic differentiation and present data to show defective depletion of CD45-null transgenic TCR-Vβ8 DP thymocytes in FTOC by the Staphylococcus aureus Enterotoxin B (SEB) superantigen.