Cell Reports (2021-02-01)

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

  • Anne Trefzer,
  • Pallavi Kadam,
  • Shu-Hung Wang,
  • Stefanie Pennavaria,
  • Benedikt Lober,
  • Batuhan Akçabozan,
  • Jan Kranich,
  • Thomas Brocker,
  • Naoko Nakano,
  • Martin Irmler,
  • Johannes Beckers,
  • Tobias Straub,
  • Reinhard Obst

Journal volume & issue
Vol. 34, no. 6
p. 108748

Abstract

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Summary: 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.

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