| First Author | Yu A | Year | 2017 |
| Journal | J Immunol | Volume | 198 |
| Issue | 8 | Pages | 3127-3135 |
| PubMed ID | 28264971 | Mgi Jnum | J:252231 |
| Mgi Id | MGI:5926114 | Doi | 10.4049/jimmunol.1601966 |
| Citation | Yu A, et al. (2017) The Lower Limit of Regulatory CD4+ Foxp3+ TCRbeta Repertoire Diversity Required To Control Autoimmunity. J Immunol 198(8):3127-3135 |
| abstractText | The TCR repertoire of regulatory T cells (Tregs) is highly diverse. The relevance of this diversity to maintain self-tolerance remains unknown. We established a model where the TCR repertoire of normal polyclonal Tregs was limited by serial transfers into IL-2Rbeta-/- mice, which lack functional Tregs. After a primary transfer, the donor Treg TCR repertoire was substantially narrowed, yet the recipients remained autoimmune-free. Importantly, upon purification and transfer of donor-derived Tregs from an individual primary recipient into neonatal IL-2Rbeta-/- mice, the secondary recipients developed autoimmunity. In this study, the Treg TCRbeta repertoire was reshaped and further narrowed. In contrast, secondary IL-2Rbeta recipients showed fewer symptoms of autoimmunity when they received donor Tregs that were premixed from several primary recipients to increase their TCRbeta repertoire diversity. About 8-11% of the Treg TCRbeta repertoire was estimated to be the minimum required to establish and maintain tolerance in primary IL-2Rbeta-/- recipients. Collectively, these data quantify where limitations imposed on the Treg TCRbeta repertoire results in a population of Tregs that cannot fully suppress polyclonal autoreactive T cells. Our data favor a model where the high diversity of the Treg TCR provides a mechanism for Tregs to actively adapt and effectively suppress autoreactive T cells, which are not fixed, but are evolving as they encounter self-antigens. |
