Greatly reduced efficiency of both positive and negative selection of thymocytes in CD45 tyrosine phosphatase-deficient mice

The T cell repertoire is shaped by positive and negative selection of thymo cytes. TCR-mediated signals that determine these selection processes are on ly partly understood. The CD45 tyrosine phosphatase has been shown to be im portant for signal transduction through the TCR, but there has been disagre ement about whether CD45 is a positive or negative regulator of TCR signali ng. Using CD45-deficient mice expressing transgenic TCR, we show that in th e absence of CD45 there is a large increase in the thresholds of TCR stimul ation required for both positive and negative selection. Our results conclu sively demonstrate that in double-positive thymocytes CD45 is a positive re gulator of the TCR signals that drive thymic selection events.