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Distinct Mechanisms Contribute to Generate and Change the CD4:CD8 Cell Ratio During Thymus Development: A Role for the Notch Ligand, Jagged1

Eva Jiménez^*, Angeles Vicente, Rosa Sacedón^*, Juan J. Muñoz^*, Gerry Weinmaster, Agustín G. Zapata^* and Alberto Varas^*

Department of Cell Biology, Faculties of ^* Biology and Medicine, Complutense University, Madrid, Spain; and Department of Biological Chemistry, School of Medicine, University of California, Los Angeles, CA 90095

In adult life, the high CD4:CD8 cell ratio observed in peripheral lymphoid organs originates in the thymus. Our results show that the low peripheral CD4:CD8 cell ratio seen during fetal life also has an intrathymic origin. This distinct production of CD4⁺CD8^- and CD4^-CD8⁺ thymocytes is regulated by the developmental age of the thymic stroma. The differential expression of Notch receptors and their ligands, especially Jagged1, throughout thymus development plays a key role in the generation of the different CD4:CD8 cell ratios. We also show that the intrathymic CD4:CD8 cell ratio sharply changes from fetal to adult values around birth. Differences in the proliferation and emigration rates of the mature thymocyte subsets contribute to this change.

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