Identifying distinct T cell subsets in the context of pediatric ARDS

Abstract

Abstract Acute respiratory distress syndrome (ARDS) is a condition defined by sudden respiratory failure caused by severe lung injury, with disease etiology that can differ across pediatric and adult patients. While T lymphocytes have been implicated in ARDS, the role of T cell subsets in pediatric ARDS (pARDS) is not fully understood. In this study, we sought to characterize the potential role of T cells in pARDS caused by viral lower respiratory tract infection (LRTI). To do this, we performed single cell RNA-Seq on tracheal aspirate samples from three categories of mechanically ventilated pediatric patients: 1) LRTI patients with pARDS, 2) LRTI patients without pARDS, and 3) ventilated patients without underlying LRTI or pARDS. All LRTI patients were diagnosed with respiratory viral infections, 70 percent of which were respiratory syncytial virus (RSV). Within the T lymphocytes, we identified populations of CD8+ T cells, CD4+ regulatory T cells, and γδ T cells that each expressed unique gene signatures with distinct distribution across disease states. We compared these data to T cell subsets within healthy lung tissue at multiple ages, and within the periphery of healthy adults. These analyses identified age, location, and disease-specific differences within T cell subsets, highlighting the unique role of T cells in pARDS. Supported by grants from NIH (R01 AI54470, R01 AI121832)