Abstract Description CD8+ T cells are an essential component of the immune response against intracellular pathogens.The influence of the fetal environment on the differentiation potential of CD8+ T cells in humans is poorly understood. In this study, we assessed the transcriptional, chromatin accessibility, and functional profile of human naïve ???? CD8+ T cells isolated from either the fetal environment (fetal spleen or cord blood) or adults (spleen or peripheral blood). We found that resting fetal naïve CD8+ T cells are transcriptionally distinct from adult naïve CD8+ T cells, and are enriched for genes expressed in human virus-specific effector CD8+ T cells (e.g., GZMM, GZMK, IRF4, CXCR3) and regulatory CD4+ T cells (e.g. TNFR2, HELIOS). Following short-term in vitro polyclonal T cell receptor (TCR) stimulation, human fetal naïve CD8+ T cells display 2-3-fold higher basal and induced levels of phosphorylated NF-κB (pS529). After four days of TCR stimulation, fetal naïve CD8+ T cells proliferate more, but clearly engage a distinct differentiation program with less upregulation of Granzyme B and T-bet and high expression of Helios and Granzymes M and K. Collectively, our study demonstrates that human fetal naïve CD8+ T cells show an altered effector differentiation potential that likely plays a unique role in shaping infant immunity to intracellular pathogens and CD8+ T cell-based vaccines. Topic Categories Hematopoiesis and Immune System Development (HEM)
Wendy Hsuan Wen Hung (Sat,) studied this question.