Impact of Absent in Melanoma 2 (AIM2) on Antigen-Specific CD4+ T cell Activation and Homeostasis

作者：Dakota M. Reinartz, Chloe Sairs, Wang Gong, Lei Ye, Michael S. Kuhns, Justin E. Wilson · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2025 · DOI：10.64898/2025.12.30.697014 · 研究领域：Immunotherapy and Immune Responses、T-cell and B-cell Immunology、Cancer Immunotherapy and Biomarkers

The intrinsic role of Absent in Melanoma 2 (AIM2) in CD4 + T cells during antigen-specific activation and differentiation is not fully understood. To address this, we crossed AIM2-deficient mice with OT-II/RAG transgenic mice, which express an ovalbumin-specific T cell receptor in CD4 + T cells (OT-II). We found that AIM2 does not regulate thymic selection of CD4 + thymocytes, but may promote trafficking or survivability of CD4 + T cells in the spleen. In vitro coculture assays revealed that Aim2 -/- OT-II CD4 + T cells produce significantly less IL-2 than wild type OT-II CD4 + T cells when cocultured with ovalbumin-incubated dendritic cells. However, we found no differences in CD4 + T cell proliferative capacity and differentiation among WT OT-II and Aim2 -/- OT-II CD4 + T cells following OVA immunization in vivo. Finally, adoptively transferred WT and Aim2 -/- OT-II cells controlled the growth of implanted OVA-expressing NOOC2 syngeneic tumors at an equal capacity. Taken together, these results indicate that AIM2 contributes to CD4 + T cell homeostasis in secondary lymphoid organs in vivo. AIM2 also intrinsically promotes IL-2 production in response to antigen-specific activation in vitro. However, this loss of IL-2 does not translate to measurable defects in proliferative, differentiation or effector function during OVA immunization or tumor challenge in vivo.