Dynamic adoption of anergy by antigen-exhausted CD4+ T cells

Anne Trefzer, Pallavi Kaam, Shu-Hung Wang, Stefanie Pennavaria, Benedikt Lober, Batuhan Akçabozan, Jan Kranich, Thomas Brocker, Naoko Nakano, Martin Irmler, Johannes Beckers, Tobias Straub, Reinhard Obst (09 Feb 2021) Dynamic adoption of anergy by antigen-exhausted CD4+ T cells. Cell Reports 34(6) 108748. DOI:https://doi.org/10.1016/j.celrep.2021.108748

Abstract cited directly from paper:

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.