Work

Aiolos restricts the generation of antigen-inexperienced, virtual memory CD8+ T cells in mice

Year: 2025

Type: article

Abstract: CD8 + virtual memory T (T VM ) cells are memory-like cells that rapidly respond to infection via antigen-independent bystander effector functions. While it is recognized that T VM cells arise independently of foreign antigen encounter, the mechanisms governing their development are not fully understood. Here, we identify the transcription factor Aiolos as a negative regulator of T VM cells. We observed higher quantities of T VM cells in the spleens of uninfected Aiolos-deficient ( Ikzf3 -/- ) mice relative to wild-type (WT). Furthermore, Ikzf3 -/- T VM cells produced higher levels of IFN-γ and granzyme B. In addition, we found that Ikzf3 -/- T VM cells accumulated to higher quantities in the lungs within 24 hours of influenza virus infection. In line with enhanced T VM functional capacity and lung trafficking, Aiolos-deficient mice cleared virus more rapidly and exhibited reduced morbidity relative to WT animals. Mechanistically, we observed that Aiolos represses the T VM transcriptional regulator Eomes and the IL-15R subunit CD122 (IL-15Rβ/IL-2Rβ), known contributors of T VM cell generation. Collectively, these findings establish Aiolos as a novel molecular repressor of T VM generation and function.

Source: Nature Communications

DOI: 10.1038/s41467-025-67540-8