DeLong Jonathan H, O'Hara Hall Aisling, Rausch Matt, Moodley Devapregasan, Perry Joseph, Park Jeongho, Phan Anthony T, Beiting Daniel P, Kedl Ross M, Hill Jonathan A, Hunter Christopher A
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Immunology Discovery Research, Janssen Research and Development, LLC, Spring House, PA 19477.
Immunohorizons. 2019 Jan 15;3(1):13-25. doi: 10.4049/immunohorizons.1800083.
Inhibitory receptors (IR) are a diverse group of cell surface molecules that modulate T cell activation, but there are gaps in our knowledge of the cell-extrinsic factors that regulate their expression. The present study found that in vivo overexpression of IL-27 in mice led to increased T cell expression of PD-L1, LAG-3, TIGIT, and TIM-3. In vitro, TCR stimulation alone promoted expression of multiple IRs, whereas IL-27 alone induced expression of PD-L1. However, the combination of intermediate TCR stimulation and IL-27 resulted in synergistic induction of LAG-3, CTLA-4, and TIGIT. In vivo, infection with resulted in parasite-specific effector T cells that expressed high levels of IR, and at local sites of infection where IL-27 production was highest, IL-27 was required for maximal effector cell expression of PD-L1, LAG-3, CTLA-4, and TIGIT. Together, these results affirm the critical role of TCR signals in the induction of IR expression but find that during infection, IL-27 promotes T cell expression of IR.
抑制性受体（IR）是一类多样的细胞表面分子，可调节T细胞活化，但我们对调节其表达的细胞外因素的了解仍存在空白。本研究发现，小鼠体内IL-27的过表达导致T细胞上PD-L1、LAG-3、TIGIT和TIM-3的表达增加。在体外，单独的TCR刺激可促进多种IR的表达，而单独的IL-27可诱导PD-L1的表达。然而，中等强度的TCR刺激与IL-27的组合可协同诱导LAG-3、CTLA-4和TIGIT的表达。在体内，感染[寄生虫名称未给出]会导致表达高水平IR的寄生虫特异性效应T细胞，在IL-27产生最高的局部感染部位，IL-27是效应细胞最大程度表达PD-L1、LAG-3、CTLA-4和TIGIT所必需的。总之，这些结果证实了TCR信号在诱导IR表达中的关键作用，但发现在感染期间，IL-27可促进T细胞IR的表达。
