The Transcription Factor Runx2 Is Required for Long-Term Persistence of Antiviral CD8+ Memory T Cells

Abstract

During acute lymphocytic choriomeningitis virus infection, pathogen-specific CD8+ cytotoxic T lymphocytes undergo clonal expansion leading to viral clearance. Following this, the majority of pathogen-specific CD8+ T cells undergo apoptosis, leaving a small number of memory CD8+ T cells that persist long-term and provide rapid protection upon secondary infection. Whereas much is known about the cytokines and transcription factors that regulate the early effector phase of the antiviral CD8+ T cell response, the factors regulating memory T cell homeostasis and survival are not well understood. In this article, we show that the Runt-related transcription factor Runx2 is important for long-term memory CD8+ T cell persistence following acute lymphocytic choriomeningitis virus–Armstrong infection in mice. Loss of Runx2 in T cells led to a reduction in KLRG1lo CD127hi memory precursor cell numbers with no effect on KLRG1hi CD127lo terminal effector cell populations. Runx2 expression levels were transcriptionally regulated by TCR signal strength via IRF4, TLR4/7, and selected cytokines. These data demonstrate a CD8+ T cell–intrinsic role for Runx2 in the long-term maintenance of antiviral memory CD8+ T cell populations.