Surfing on the waves of the human γδ T cell ontogenic sea

Abstract

γδ T cells are, like αβ T cells and B cells, lymphocytes that can rearrange gene segments at the DNA level with the potential to generate a set of highly diverse antigen receptors. 1,2 This tripartite division of immune cells possessing somatically diversified antigen receptors (γδ T cell receptor (TCR), αβ TCR and B cell receptor (BCR)) is a fundamental pillar of the immune system in jawed vertebrates (Gnathostomata). 3 Indeed, this division is traced back even in distant species with cryptic lymphocyte lineages, such as cartilaginous fish (Chondrichthyes), 4 and a similar division pattern can be observed in jawless vertebrates (Agnatha), despite arising from a distinct somatic recombination system that originates around 500 million years ago. 5 This striking conservation emphasizes the non-redundant roles of γδ

Layered immune system development in mice and humans

“…Their review is distinguished by an elegant genetic analysis of genome‐wide transcription data that has become available in recent years. As noted above, the single cell human sequencing studies have also revealed differences in gene expression in waves of human γδ T cell development as discussed by Sanchez et al 22 …”

“…Their review is distinguished by an elegant genetic analysis of genome-wide transcription data that has become available in recent years. As noted above, the single cell human sequencing studies have also revealed differences in gene expression in waves of human γδ T cell development as discussed by Sanchez et al 22 At least two models can be formulated to explain the layering of immune and hematopoietic system development (Figure 1). The An alternative "Molecular Layering model" is presented in the review from Burt and McCune.…”

“…The results discussed above were obtained from analysis of mice, but there is evidence that layering of immune system development also occurs in humans as presented in three reviews in this issue of Immunological Reviews . Sanchez et al 22 discuss single cell sequencing results that support the existence of several distinct functional waves of γδ T cell development in the human fetal thymus. They also review the role of Lin28b and additional intrinsic and extrinsic factors in driving the fetal γδ T cell receptor repertoire in human γδ thymocytes.…”

“…The results discussed above were obtained from analysis of mice, but there is evidence that layering of immune system development also occurs in humans as presented in three reviews in this issue of Immunological Reviews. Sanchez et al 22 However, whether the layering of immune system development in humans is as extensive as in mice is unclear. For example, it has been challenging to identify human B-1 B cell progenitors.…”

Early-life thymectomy enhances persistence of fetal-derived γδ T cells in children with congenital heart disease

“…11,12 In fact, previous studies reported that reduced thymic activity leads to changes in the immune cell composition in patients with CHD, including lower total numbers of T cells, [13][14][15] lower frequencies of naïve CD4 + and CD8 + αβ T cells, 16 and less diversity in the T cell receptor (TCR) repertoire of αβ T cells. 17 However, T cells that predominantly develop in the prenatal thymus, 18,19 have not been the focus of studies in this context.…”