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| Item Type: | Article |
|---|---|
| Title: | Thymus-derived regulatory T cells are positively selected on natural self-antigen through cognate interactions of high functional avidity |
| Creators Name: | Kieback, E., Hilgenberg, E., Stervbo, U., Lampropoulou, V., Shen, P., Bunse, M., Jaimes, Y., Boudinot, P., Radbruch, A., Klemm, U., Kühl, A.A., Liblau, R., Hoevelmeyer, N., Anderton, S.M., Uckert, W. and Fillatreau, S. |
| Abstract: | Regulatory T (Treg) cells expressing Foxp3 transcripton factor are essential for immune homeostasis. They arise in the thymus as a separate lineage from conventional CD4(+)Foxp3(-) T (Tconv) cells. Here, we show that the thymic development of Treg cells depends on the expression of their endogenous cognate self-antigen. The formation of these cells was impaired in mice lacking this self-antigen, while Tconv cell development was not negatively affected. Thymus-derived Treg cells were selected by self-antigens in a specific manner, while autoreactive Tconv cells were produced through degenerate recognition of distinct antigens. These distinct modes of development were associated with the expression of T cell receptor of higher functional avidity for self-antigen by Treg cells than Tconv cells, a difference subsequently essential for the control of autoimmunity. Our study documents how self-antigens define the repertoire of thymus-derived Treg cells to subsequently endow this cell type with the capacity to undermine autoimmune attack. |
| Keywords: | Autoantigens, CTLA-4 Antigen, Cultured Cells, Antigen-Mediated Clonal Selection, Experimental Autoimmune Encephalomyelitis, Forkhead Transcription Factors, Inbred C57BL Mice, Knockout Mice, Multiple Sclerosis, Myelin-Oligodendrocyte Glycoprotein, Peptide Fragments, T-Cell Antigen Receptors, T-Cell Antigen Receptor Specificity, T-Lymphocyte Subsets, Regulatory T-Lymphocytes, Thymus Gland, Animals, Mice |
| Source: | Immunity |
| ISSN: | 1074-7613 |
| Publisher: | Cell Press / Elsevier |
| Volume: | 44 |
| Number: | 5 |
| Page Range: | 1114-1126 |
| Date: | 17 May 2016 |
| Official Publication: | https://doi.org/10.1016/j.immuni.2016.04.018 |
| PubMed: | View item in PubMed |
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