| Title: |
CD8 T cell tolerance results from eviction of immature autoreactive cells from the thymus. |
| Authors: |
Badr, Mohamed Elsherif; Zhongmei Zhang; Xuguang Tai; Singer, Alfred |
| Source: |
Science (pre-March 2025); 11/3/2023, Vol. 382 Issue 6670, p534-541, 8p, 1 Color Photograph, 4 Diagrams |
| Subject Terms: |
T cells; CD8 antigen; Thymus; Eviction; Myasthenia gravis; Thymocytes; T cell receptors |
| Abstract: |
CD8 T cell tolerance is thought to result from clonal deletion of autoreactive thymocytes before they differentiate into mature CD8 T cells in the thymus. However, we report that, in mice, CD8 T cell tolerance instead results from premature thymic eviction of immature autoreactive CD8 thymocytes into the periphery, where they differentiate into self-tolerant mature CD8 T cells. Premature thymic eviction is triggered by T cell receptor (TCR)–driven down-regulation of the transcriptional repressor Gfi1, which induces expression of sphingosine-1–phosphate receptor-1 (S1P1) on negatively selected immature CD8 thymocytes. Thus, premature thymic eviction is the basis for CD8 T cell tolerance and is the mechanism responsible for the appearance in the periphery of mature CD8 T cells bearing autoreactive TCRs that are absent from the thymus. [ABSTRACT FROM AUTHOR] |
| : |
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| Database: |
Complementary Index |