Complementary models of thymic disruption reveal novel neonatal-like T cell responses to Bordetella pertussis 2355

Abstract Description The immune system of neonates is vastly different from that of adults and often associated with increased susceptibility to some pathogens. One of the most important aspects of this susceptibility is the transition from neonatal to perinatal immune responses. This process is primarily driven by thymus development and the T cells generated; however, the contribution of T cells generated during this process to control of pathogens is poorly understood. Unfortunately, attempts to understand the roles of T cells developed at various stages are often confounded by the rapid development of the thymus in mice. Here, we utilize two complementary models of disrupted thymic development to assess the effects of thymic development on responses to a neonatal pathogen, Bordetella pertussis (Bp). Utilizing a genetic model of disrupted thymic development, we show that post-birth thymus development is critical for controlling Bp. With a complementary surgical model, mice thymectomized at P0 and P7 had substantially different T cell responses to Bp, with the later demonstrating an early CD8 response associated with more rapid control. These two models agree that T cells generated at distinct stages of development demonstrate different contributions to control of Bp. Further work to understand the functions of T cells generated at each developmental phase, and their roles in pathogen defense can greatly improve our understanding of the neonatal immune system. Funding Sources This work was supported by National Institutes of Health Grants AI149787, DC018496, AI156293, AI159347, and AI139449. Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)