Institute of Microbiology, ETH Zurich, Wolfgang-Pauli-Str. 10, 8093 Zurich, Switzerland.
Trends Immunol. 2013 May;34(5):193-9. doi: 10.1016/j.it.2012.12.002. Epub 2013 Jan 16.
The identification of T cell co-inhibition as a central mechanism in the regulation of adaptive immunity during infectious diseases provides new opportunities for immunotherapeutic interventions. However, the fact that T cell activity is frequently downregulated during pathogen-directed responses suggests a pivotal physiological role of co-inhibitory pathways during infectious disease. Reports of exacerbated immunopathology in conditions of impaired co-inhibition foster the view that downregulation of T cell activity is an essential negative feedback mechanism that protects from excessive pathogen-directed immunity. Thus, targeting co-inhibitory pathways can bear detrimental potential through the deregulation of physiological processes. Here, we summarize recent preclinical and clinical interventions that report immune-related adverse events after targeting co-inhibitory pathways.
T 细胞共抑制的鉴定作为感染性疾病中适应性免疫调节的中心机制，为免疫治疗干预提供了新的机会。然而，在病原体定向反应过程中 T 细胞活性经常被下调的事实表明，共抑制途径在感染性疾病中具有关键的生理作用。在共抑制受损的情况下，免疫病理学加重的报告支持这样一种观点，即 T 细胞活性的下调是一种防止过度病原体定向免疫的必要负反馈机制。因此，通过调节生理过程，靶向共抑制途径可能具有潜在的有害性。在这里，我们总结了最近的临床前和临床干预措施，这些措施报告了靶向共抑制途径后的免疫相关不良事件。
