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Abstract
This study investigated the molecular mechanisms through which OX40 stimulation enhances T‑cell function. Gene expression profiling of OX40‑activated antigen‑specific T cells suggested involvement of the transcription factor c‑Myc and its antagonists Mad4 and Mnt. Using an adoptive transfer model of OVA‑specific DO11.10 T cells in BALB/c mice, we found that OX40 engagement increased T‑cell proliferation and survival. Western blot analyses showed that Mad4, Mnt, and c‑Myc were upregulated early after OX40 stimulation, with OX40 signaling stabilizing Mad4 and Mnt proteins by preventing their degradation. siRNA knockdown of Mad4 and Mnt reduced survival of OX40‑activated T cells, indicating these proteins help counterbalance c‑Myc–driven activation and support memory T‑cell development.