Combination immunotherapy (CIT) is currently applied as a treatment for different cancers and is proposed as a cure strategy for chronic viral infections. Whether such therapies are efficient during an acute infection remains elusive. To address this, inhibitory receptors were blocked and regulatory T cells depleted in acutely Friend retrovirus-infected mice. CIT resulted in a dramatic expansion of cytotoxic CD4+ and CD8+ T cells and a subsequent reduction in viral loads. Despite limited viral replication, mice developed fatal immunopathology after CIT. The pathology was most severe in the gastrointestinal tract and was mediated by granzyme B producing CD4+ and CD8+ T cells. A similar post-CIT pathology during acute Influenza virus infection of mice was observed, which could be prevented by vaccination. Melanoma patients who developed immune-related adverse events under immune checkpoint CIT also presented with expanded granzyme-expressing CD4+ and CD8+ T cell populations. Our data suggest that acute infections may induce immunopathology in patients treated with CIT, and that effective measures for infection prevention should be applied.

组合免疫疗法（CIT）目前被用于治疗不同的癌症，并被提议作为慢性病毒感染的治疗策略。这种疗法在急性感染期间是否有效尚不清楚。为了解决这个问题，在急性Friend逆转录病毒感染的小鼠中抑制性受体被阻断并且调节性T细胞被耗尽。CIT导致细胞毒性CD4 +和CD8 + T细胞急剧扩增，并随后减少了病毒载量。尽管病毒复制受到限制，但小鼠在CIT后仍会发生致命的免疫病理。病理在胃肠道中最严重，并且由产生CD4 +和CD8 + T细胞的粒酶B介导。观察到小鼠急性流感病毒感染期间的类似CIT后病理，可以​​通过接种疫苗预防。在免疫检查点CIT下发生免疫相关不良事件的黑色素瘤患者也表现出表达颗粒酶的CD4 +和CD8 + T细胞群增加。我们的数据表明，急性感染可能会在接受CIT治疗的患者中诱发免疫病理，因此应采取有效的预防感染措施。