| First Author | Trefzer A | Year | 2021 |
| Journal | Cell Rep | Volume | 34 |
| Issue | 6 | Pages | 108748 |
| PubMed ID | 33567282 | Mgi Jnum | J:313874 |
| Mgi Id | MGI:6706255 | Doi | 10.1016/j.celrep.2021.108748 |
| Citation | Trefzer A, et al. (2021) Dynamic adoption of anergy by antigen-exhausted CD4(+) T cells. Cell Rep 34(6):108748 |
| abstractText | Exhausted immune responses to chronic diseases represent a major challenge to global health. We study CD4(+) T cells in a mouse model with regulatable antigen presentation. When the cells are driven through the effector phase and are then exposed to different levels of persistent antigen, they lose their T helper 1 (Th1) functions, upregulate exhaustion markers, resemble naturally anergic cells, and modulate their MAPK, mTORC1, and Ca(2+)/calcineurin signaling pathways with increasing dose and time. They also become unable to help B cells and, at the highest dose, undergo apoptosis. Transcriptomic analyses show the dynamic adjustment of gene expression and the accumulation of T cell receptor (TCR) signals over a period of weeks. Upon antigen removal, the cells recover their functionality while losing exhaustion and anergy markers. Our data suggest an adjustable response of CD4(+) T cells to different levels of persisting antigen and contribute to a better understanding of chronic disease. |
