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 KLRG1^lo CD127^hi memory precursor cell numbers with no effect on KLRG1^hi CD127^lo 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.