Intraclonal competition limits the fate determination of regulatory T cells in the thymus
| Autor: | Chan-Wang J. Lio, Chyi-Song Hsieh, Jingqin Luo, Stephanie K. Lathrop, Katherine A. Forbush, Jhoanne L. Bautista, Yuqiong Liang, Alexander Y. Rudensky |
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| Rok vydání: | 2009 |
| Předmět: |
Cellular differentiation
Immunology Receptors Antigen T-Cell Bone Marrow Cells Mice Transgenic chemical and pharmacologic phenomena Thymus Gland Biology medicine.disease_cause T-Lymphocytes Regulatory Autoimmunity Mice Chimera (genetics) Antigen medicine Animals Immunology and Allergy Cytotoxic T cell Receptor Mice Knockout Chimera T-cell receptor FOXP3 Cell Differentiation Forkhead Transcription Factors hemic and immune systems Cell biology Genes T-Cell Receptor beta |
| Zdroj: | Nature Immunology. 10:610-617 |
| ISSN: | 1529-2916 1529-2908 |
| Popis: | Because the deletion of self-reactive T cells is incomplete, thymic development of natural Foxp3+CD4+ regulatory T cells (Treg cells) is required for preventing autoimmunity. However, the function of T cell antigen receptor (TCR) specificity in thymic Treg cell development remains controversial. To address this issue, we generated a transgenic line expressing a naturally occurring Treg cell-derived TCR. Unexpectedly, we found that efficient thymic Treg cell development occurred only when the antigen-specific Treg cell precursors were present at low clonal frequency (o1%) in a normal thymus. Using retroviral vectors and bone marrow chimeras, we observed similar activity with two other Treg cell-derived TCRs. Our data demonstrate that thymic Treg cell development is a 'TCR-instructive' process involving a niche that can be saturable at much lower clonal frequencies than is the niche for positive selection. |
| Databáze: | OpenAIRE |
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