Stepwise differentiation from precursor intermediates and distinct Th1 checkpoints promote CD4 Th1 cell differentiation during chronic viral infection.

ABSTRACT: CD4⁺ helper T cells are essential for controlling viral infections. During chronic LCMV infection, CD4⁺ T cells differentiate into heterogeneous populations, including a TCF-1^hi progenitor subset that serves as a reservoir to continuously replenish type 1 helper (Th1) and follicular helper (Tfh) T cells. The gradual loss of CD4⁺ Th1 cell responses impairs the immune system's ability to control viral replication and contributes to the development of CD8⁺ T cell exhaustion. However, the mechanisms directing Th1 differentiation and the factors underlying their progressive decline during chronic infection remain poorly understood. In this study, we delineate the stepwise differentiation trajectory of Th1 cells, tracing their progression fr

SUBMITTER: Niu H 

PROVIDER: S-EPMC12867724 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature