Single-cell RNA-seq analysis identifies the atlas of lymph fluid and reveals a sepsis-related T cell subset

The lymphoid cycle serves as a sentinel of the immune response, yet the cell subtypes and immune properties within lymph fluid remain unclear. This study describes a comprehensive characterization of immune cells in rat lymph fluid using single-cell RNA sequencing, identifying a unique subset of CD4⁺ T cells (CD4_Icos) that suppresses inflammation in early sepsis. Trajectory analysis reveals that CD4+Icos+ T cells can differentiate into regulatory T cells (Tregs). Transferring CD4+Icos+ T cells alleviates CLP-induced organ injury, while CD4⁺ Icos-knockout (KO) mice show reduced Treg numbers, increased inflammation, and higher mortality. Further experiments identify Npas2 as an Icos-specific transcription factor regulating Icos expression and promoting the differentiation of CD4+Icos+ T cells. Clinical data show a negative correlation between ICOS expression in CD4⁺ T cells and clinical outcomes in septic patients. These findings highlight the protective role of CD4⁺ T cells in modulating immune responses and mitigating sepsis progression.