Figure 1.

Models of human immune development. Throughout different stages of development, fetal T and myeloid cells, as compared to their adult counterparts, specifically populate a subset of tissues including the epithelium (DETC, non-DETC cells, and Langerhans cells), the brain (microglia), and the heart (cardiac macrophages). This differential population of tissues depending on developmental stage suggests that immune maturation does not proceed in a linear fashion and is rather a specifically timed layering of cells with distinct functions, giving rise to specialized tissue-resident populations. (A) Linear model of immune development. Previous work suggested that the fetal immune system is completely naïve. After birth, it is exposed to massive antigenic doses and matures into the adult immune system. (B) The layered model of immune development. Several types of HSPC appear sequentially and function at specific times during development in a cell autonomous manner, creating unique layers of HSPC-derived cells with different functional outcomes. During gestation, cells are derived from a fetal HSPC and have a specific functional outcome; while in the adult, the vast majority of the cells come from an adult HSPC that has an adult functional outcome. This model suggests that there is a period between 20 gestational weeks and 6 months to a year after birth where there is an admixture of fetal and adult-derived cells, and that it is this admixture of functionally different cell populations that gives rise to inter-individual differences observed in the neonatal immune response. (C) The maturation model of immune development. Fetal cells mature into adult cells such that at birth there are cells with a mixture of both fetal and adult characteristics.