Fetal Exposure to High-Avidity TCR Ligand Enhances Expansion of Peripheral T Regulatory Cells
| Autor: | Jason A. Cascio, Renu Jain, Austin Ostermeier, John C. Hardaway, Rohit D. Divekar, Cara L. Haymaker, Habib Zaghouani, Ping Yu, Danielle M. Tartar, Jason S. Ellis, Christine M. Hoeman |
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| Rok vydání: | 2008 |
| Předmět: |
Encephalomyelitis
Autoimmune Experimental Cellular differentiation Immunology Receptors Antigen T-Cell Immunoglobulins chemical and pharmacologic phenomena Ligands medicine.disease_cause T-Lymphocytes Regulatory Article Epitope Autoimmunity Mice Fetus medicine Animals Immunology and Allergy Lymphocyte Count Thymic T cell selection biology T-cell receptor Peripheral tolerance Cell Differentiation hemic and immune systems Immunity Innate biology.protein Antibody |
| Zdroj: | The Journal of Immunology. 181:73-80 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Lately, it has become clear that regulatory T cells (Tregs) play a major role in the maintenance of peripheral tolerance and control of autoimmunity. Despite these critical functions, the process underlying the development of Tregs remains largely undefined. Herein, altered peptide ligand (APL) variants derived from the proteolipid protein-1 (PLP1) epitope were expressed on immunoglobulins (Igs) and the resulting Ig-APLs were used to deliver the APLs from mother to fetus through the maternal placenta to influence thymic T cell selection. This delivery system was then adapted to the SJL/J mouse, a strain that expresses only the DM20 form of PLP, which lacks the dominant PLP1 epitope in the thymus during fetal and neonatal development. This model, which restores thymic T cell selection for PLP1, was then used to determine whether affinity plays a role in the development of Tregs. The findings show that fetal exposure to low-affinity peptide ligand was unable to drive development of Tregs while variants with higher affinity to the TCR resulted in significant seeding of the periphery with mature, naive Tregs. Thus, contrary to pathogenic T cells, Tregs require avid TCR-ligand interaction to undergo thymic development and maturation. |
| Databáze: | OpenAIRE |
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