Date of Award
Fall 2023
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Immunobiology
First Advisor
Lucas, Carrie
Abstract
Children and babies have unique infectious and inflammatory susceptibilities and are at an increased risk for developing severe disease or autoinflammatory sequelae from infections. However, many pediatric autoinflammatory diseases are poorly understood, as are mechanisms by which humans mount immune defenses in early life. We uncovered novel immunopathologic mechanisms underlying two childhood inflammatory conditions linked to COVID-19 infection and vaccination: multisystem inflammatory syndrome in children (MIS-C) and vaccine-adjacent myopericarditis, respectively. We leveraged a systems approach to study these conditions, using multiomic single-cell RNA sequencing and serum profiling. We found key signatures of MIS-C that include innate immune triggering, and an expansion of cytotoxic and proliferating TRBV11-2+ T cells in patients with severe disease. Similarly, we found a a polyclonal expansion of activated T cells in myopericarditis, likely driven by systemic cytokinopathy. Finally, to understand more about immune defenses in very early life, we conducted a study of natural killer (NK) cells in neonates. We found that neonatal NK cells expressed molecules associated with cytotoxicity, and when exposed to NK-activating cytokines, exhibited increased proliferative and cytolytic activity compared to adult cells. Collectively, these studies reveal key features of early life immunity and inflammation. These findings may not only inform treatment of COVID-19-related inflammatory diseases, but may also contribute to our understanding of the immune system in early life.
Recommended Citation
Ramaswamy, Anjali, "Mechanisms of Immunopathology Following COVID-19 and Vaccination in Children & Early Life Immunity in Neonates" (2023). Yale Graduate School of Arts and Sciences Dissertations. 1152.
https://elischolar.library.yale.edu/gsas_dissertations/1152
