Distinct mechanisms contribute to generate and change the CD4:CD8 cell ratio during thymus development: a role for the Notch ligand, Jagged1.
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.
Jiménez
E
E
Department of Cell Biology, Faculties of Biology, Complutense University, Madrid, Spain.
Vicente
A
A
Sacedón
R
R
Muñoz
J J
JJ
Weinmaster
G
G
Zapata
A G
AG
Varas
A
A
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D016516:CD4-CD8 Ratio; D002135:Calcium-Binding Proteins; D016923:Cell Death / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D016922:Cellular Senescence / Q000276:immunology; D005314:Embryonic and Fetal Development / Q000276:immunology; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology; D016130:Immunophenotyping; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008024:Ligands; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000378:metabolism*; D009924:Organ Culture Techniques; D011506:Proteins / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology / Q000254:growth & development / Q000378:metabolism
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606275:Jag1 protein, rat; D000072100:Jagged-1 Protein; D008024:Ligands; D008565:Membrane Proteins; D011506:Proteins; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins