Though myocardial infarction (MI) in pigs is a well-established translational large animal model, it has not yet been widely used for immunotherapy studies, and a comprehensive description of the immune response to MI in this species is lacking. We induced MI in Landrace pigs by balloon occlusion of the left anterior descending artery over 90 min. Within 14 days, the necrotic myocardium was progressively replaced by scar tissue with involvement of myofibroblasts. We characterized the immune response in the heart ex vivo by (immuno)histology, flow cytometry, and RNA sequencing of myocardial tissue on days 3, 7, and 14 after MI. Besides a clear predominance of myeloid cells among heart-infiltrating leukocytes, we detected activated T cells and an increasing proportion of CD4⁺ Foxp3⁺ regulatory T cells (T_reg), especially in the infarct core—findings that closely mirror what has been observed in mice and humans after MI. Transcriptome data indicated inflammatory activity that was persistent but markedly changing in character over time and linked to extracellular matrix biology. Analysis of lymphocytes in heart-draining lymph nodes revealed significantly higher proliferation rates of T helper cell subsets, including T_reg on day 7 after MI, compared to sham controls. Elevated frequencies of myeloid progenitors in the spleen suggest that it might be a site of emergency myelopoiesis after MI in pigs, as previously shown in mice. We thus provide a first description of the immune response to MI in pigs, and our results can aid future research using the species for preclinical immunotherapy studies.

尽管猪心肌梗死（MI）是一种成熟的转化大型动物模型，但尚未广泛用于免疫治疗研究，并且缺乏对该物种对 MI 免疫反应的全面描述。我们通过球囊闭塞左前降支 90 分钟来诱导长白猪心肌梗死。 14天内，坏死的心肌逐渐被疤痕组织所取代，并伴有肌成纤维细胞的参与。我们通过心肌梗死后第 3、7 和 14 天的心肌组织的（免疫）组织学、流式细胞术和 RNA 测序来表征离体心脏的免疫反应。除了心脏浸润白细胞中髓系细胞明显占主导地位外，我们还检测到活化的 T 细胞和 CD4 ⁺ Foxp3 ⁺调节性 T 细胞 (T _reg ) 比例不断增加，特别是在梗塞核心中，这一发现与在MI 后的小鼠和人类。转录组数据表明炎症活动是持续存在的，但随着时间的推移其特征发生显着变化，并且与细胞外基质生物学有关。对心脏引流淋巴结中淋巴细胞的分析显示，与假手术对照组相比，辅助性 T 细胞亚群（包括 MI 后第 7 天的T _reg）的增殖率明显更高。脾脏中骨髓祖细胞频率的升高表明，正如之前在小鼠中所显示的那样，脾脏可能是猪心肌梗死后紧急骨髓细胞生成的部位。因此，我们首次描述了猪对 MI 的免疫反应，我们的结果可以帮助未来使用该物种进行临床前免疫治疗研究。