Distinct sequence of negative or positive selection implied by thymocyte T-cell receptor densities

Abstract
RECENT evidence suggests that positive and negative selection of thymocytes bearing αβ T-cell receptors occurs during the predominant double-positive (CD4+CD8+) stage1–13. But the sequence or stage at which positive or negative selection occurs during thymocyte maturation has not been well defined14,15. Here we use transgenic mice to show that the CD4+CD8+ stage might be further subdivided into CD3l0 (low) and CD3in (intermediate) stages. The CD3in stage could represent T cells that have been positively selected, as this stage is dependent on the presence of the appropriate major histocompatiblilty complex restriction element. In addition, we use two different tolerizing antigens to show that negative selection may occur either before or after this CD3in stage.