Abstract
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 Ca2+/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.
Item Type: | Journal article |
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Faculties: | Medicine |
Subjects: | 600 Technology > 610 Medicine and health |
ISSN: | 2211-1247 |
Language: | English |
Item ID: | 102638 |
Date Deposited: | 05. Jun 2023, 15:40 |
Last Modified: | 17. Oct 2023, 15:11 |