Dynamic expression of IL-21 in effector CD8 T cells helps control chronic infections.

Authors

Zixuan Zhao, Han Feng, Xiaohong Zhao, Bowen Xie, Tian Xie, Qinli Sun, Yongzhen Chen, Kun Wei, Birui Pan, Peng Wei, Xuan Zhong, Lei Yuan, Xue Bai, Xiaohu Wang, Chen Dong

Published in

Science immunology. Volume 11. Issue 121. Pages eaec5171. Jul 31, 2026. Epub Jul 31, 2026.

Abstract

CD8 T cells are critical players in immune responses against pathogens. Interleukin-21 (IL-21) is predominantly produced by CD4 T cells and exerts multifaceted effects on CD8 T cell regulation and function. Using Il21-reporter and Il21-fate mapping mice, we report that a subpopulation of activated CD8 T cells also produces IL-21 in the context of lymphocytic choriomeningitis virus (LCMV) infection. During the early effector phase of both acute and chronic infections, IL-21-expressing CD8 T cells exhibit substantial proliferative and cytotoxic capacities, with higher levels of interferon-γ (IFN-γ) and granzyme B (GZMB) compared with IL-21^- counterparts. Moreover, CD8 T cell-derived IL-21 played a critical protective role in chronic, but not acute, infection. IL-21 expression in CD8 T cells appeared to be largely restricted to exhausted progenitor T cells during the exhaustion phase of chronic infection. These findings identify IL-21-expressing CD8 T cells as pivotal players in the control of chronic infection.

PMID:
42536711
Bibliographic data and abstract were imported from PubMed on 01 Aug 2026.

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