Early life development of the human gut immune system 4505

Abstract Description Early life is a critical period for generating robust immune response against harmful pathogens while simultaneously inducing tolerance to innocuous antigen. The gut is a major site for these early immune exposures, particularly in Peyer’s patches (PP), though the process in humans remains uncharacterized. Here, we examined human small intestine and associated PPs obtained from pediatric organ donors aged 0 – 10 years to investigate immune development, focusing on the T and B cell interactions, using a combination of immunofluorescence microscopy, flow cytometry, and single-cell RNA transcriptome profiling. We identified robust follicular activity characterized by early formation of germinal centers (GC) in the PP and mesenteric lymph nodes (MLN), which peaked at 2 years of age before declining. The proportion of class-switched memory B cells (MBC) increased in the tissues over early life. Although PP and MLN are primary sources of IgA-producing cells, a significant amount of IgG-expressing B cells was also generated. Interestingly, flow cytometry showed increases in follicular helper T cells (Tfh) and regulatory T cells (Treg) prior to the peak in GC response. Our data indicate that, in situ, adaptive immune responses in the infants are predominantly active in the early years of life, with important implications for designing strategies for targeting mucosal responses in vaccines and immunotherapies. Funding Sources Supported by NIH AI168634, grants from the Helmsley Charitable Trust, and 2018PGV1D071. Topic Categories Hematopoiesis and Immune System Development (HEM)