WIP 80 - Differences in T Cell and Myeloid Derived Suppressor Cell Function in Children with Severe Lower Respiratory Infections Requiring Hospitalization

Publication Number: WIP 80.7649

Rebecca M. Glowinski, Nationwide Children's Hospital, Columbus, OH, United States; Emily Ernest, Nationwide Children’s Hospital, Grandview Heights, OH, United States; Sara E. Mertz, Nationwide Children's Hospital, Columbus, OH, United States; Lisa M. Steele, Nationwide Children's Hospital, Columbus, OH, United States; Jill Popelka, Nationwide Children's Hospital, Columbus, OH, United States; Dylan Brown, Nationwide Children's Hospital, Columbus, OH, United States; Julie Rice-Weimer, Nationwide Children's Hospital, Columbus, OH, United States; Katherine Bline, Nationwide Children's Hospital, Columbus, OH, United States

Background: Lower respiratory tract infection (LRTI) is the leading cause of death in children < 1 year, and the second leading cause of death in children 1-4 years, worldwide. While some young children and infants can clear LRTIs with minimal intervention, others require hospitalization and more invasive supportive measures including mechanical ventilation. Many children requiring hospitalization have no known risk factors prior to developing severe disease. Children with severe LRTI can develop a dysregulated immune response with an exaggerated anti-inflammatory response that is associated with worse outcomes. Myeloid derived suppressor cells (MDSC) are increasingly being investigated for their role in permitting severe disease. MDSC suppress immune cell responses via direct signaling and indirect secretion of molecules.

Objective: We hypothesize that children requiring hospitalization for LRTI with more severe disease have overly suppressive MDSC responses leading to hypoactive T cell responses, and severe disease phenotypes. This study aims to characterize the role of MDSC-mediated T cell suppression in moderate/severe LRTI requiring hospitalization by correlating cell subtypes with viral and disease severity characteristics.

Design/Methods: We prospectively enrolled children hospitalized for viral LRTI, alongside a cohort of healthy control children. Demographic, viral, and clinical severity information was collected from the electronic health record. PBMC were collected for flow cytometric analysis of circulating T cell and MDSC proportions. These samples were also stained for markers of MDSC-mediated suppression including programmed death- ligand 1(PD-L1) and arginase-1 (Arg-1), and T cell markers of suppression (PD-1) and activation (inducible costimulatory, ICOS). Proportions of overall, and activated and suppressed, cell type subsets were compared based on demographic, viral, and disease severity characteristics. This study has been approved by the NCH IRB (#10-00028) and sample collection has begun. Data analysis will be conducted from November 2024 to April 2025.