Human fetal T cells: Insights into developmental specialization and mechanisms of lineage transition

Abstract

This article is part of a series of reviews covering Ontogenic Waves of Immune Cell Development appearing in Volume 315 of Immunological Reviews.

Layered immune system development in mice and humans

“…Their chapter provides an overview of single cell sequencing results which support the existence of distinct ontogenic populations of CD8 T cells in humans. Burt and McCune 24 present a detailed review that also supports the layered development of human CD8 as well as CD4 T cells.…”

“…In fact, studies of early human lympho‐hematopoiesis are challenging, because it is not easy to obtain human fetal tissues, particularly at precisely timed stages of development as discussed by Burt and McCune 24 . In addition, they point out that the sophisticated lineage tracing models that have been used in mice, discussed in the various chapters herein and the review from Van de Parvet 15 in particular, are not available.…”

“…An alternative “Molecular Layering model” is presented in the review from Burt and McCune 24 . Based on single cell sequencing of human cord blood HSPCs and T cells, those investigators concluded that the stem and progenitor cell pool in the fetus is relatively homogeneous and that, at least from the perspective of T cell development, “the transition from human fetal to adult T cell identity and function does not occur due to a switch between distinct fetal and adult lineages.…”

“…These observations raise the question of what regulates changes in gene expression in a fetal HSPC as it takes up residence in the adult? One possibility, as discussed by Burt and McCune, 24 is that HSPCs possesses an internal clock that coordinates changes in gene expression over time. Alternatively, changes in the environments stem cells occupy may trigger changes in gene expression.…”

Effects of extremely preterm birth on cytokine and chemokine responses induced by T‐cell activation during infancy

“…15,16 However, the functional capacity of T cells to respond to activating signals has yet to be determined in EPT infants. [17][18][19] The composition of the gut microbiota during the initial months after birth critically influences immune maturation, 20 and an impaired gut microbiota development has been observed in preterm infants. 21 Hence, promoting the establishment of a beneficial gut microbiota early in life may improve health outcomes in this vulnerable population.…”