CD4 + CD25 + Foxp3 + regulatory T cell formation requires more specific recognition of a self-peptide than thymocyte deletion
| Autor: | Cristina Cozzo Picca, Olivia A. Perng, Elizabeth Kropf, Jan Erikson, Christina Mergenthaler, Malinda Aitken, Andrew J. Caton, Donald M. Simons, Soyoung Oh |
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| Rok vydání: | 2011 |
| Předmět: |
Agonist
medicine.drug_class Regulatory T cell Receptors Antigen T-Cell chemical and pharmacologic phenomena Thymus Gland Biology Major histocompatibility complex T-Lymphocytes Regulatory Mice Histocompatibility Antigens medicine Animals IL-2 receptor Receptor Mice Inbred BALB C Multidisciplinary T-cell receptor Models Immunological FOXP3 hemic and immune systems Biological Sciences Cell biology Thymocyte medicine.anatomical_structure Immunology biology.protein Peptides |
| Zdroj: | Proceedings of the National Academy of Sciences. 108:14890-14895 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1103810108 |
| Popis: | CD4 + CD25 + Foxp3 + regulatory T (Treg) cells are generated during thymocyte development and play a crucial role in preventing the immune system from attacking the body's cells and tissues. However, how the formation of these cells is directed by T-cell receptor (TCR) recognition of self-peptide:major histocompatibility complex (MHC) ligands remains poorly understood. We show that an agonist self-peptide with which a TCR is strongly reactive can induce a combination of thymocyte deletion and CD4 + CD25 + Foxp3 + Treg cell formation in vivo. A weakly cross-reactive partial agonist self-peptide could similarly induce thymocyte deletion, but failed to induce Treg cell formation. These studies indicate that CD4 + CD25 + Foxp3 + Treg cell formation can require highly stringent recognition of an agonist self-peptide by developing thymocytes. They also refine the “avidity” model of thymocyte selection by demonstrating that the quality of the signal mediated by agonist self-peptides, rather than the overall intensity of TCR signaling, can be a critical factor in directing autoreactive thymocytes to undergo CD4 + CD25 + Foxp3 + Treg cell formation and/or deletion during their development. |
| Databáze: | OpenAIRE |
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