Human Recent Thymic Emigrants–Identification, Expansion, And Survival Characteristics

Abstract

This study shows that, in humans at birth, circulating T cells represent recent thymic emigrants (RTEs) as reflected in their high level of expression of TCR excision circles. RTEs express “thymocyte-like” characteristics with regard to rapid rate of apoptosis. In the presence of common γ-chain cytokines, in particular IL-7, they show enhanced potential to survive, entry into cell cycle, and proliferation. Although common γ-chain cytokines were also potent antiapoptotic stimuli for mature adult-derived naive CD4+CD45RA+ T cells, these cells were refractory to IL-7-induced expansion in vitro. RTEs cultured with IL-7 could not reinduce recombination-activating gene-2 gene expression in vitro. These data suggest that postthymic naive T cells in the periphery during early life are at a unique stage in ontogeny as RTEs, during which they can undergo homeostatic regulation including expansion and survival in an Ag-independent manner while maintaining their preselected TCR repertoire.

IL-7-Regulated Homeostatic Maintenance of Recent Thymic Emigrants in Association with Caspase-Mediated Cell Proliferation and Apoptotic Cell Death

“…These cytokines, which include IL-2, IL-4, and IL-7, play a vital role in the development, expansion, and survival of the lymphoid system (11). Previous work by our group and others has shown that IL-7 can induce expansion and survival of these cells while maintaining a naive phenotype (6,10,12). The antiapoptotic effect of IL-7 has been shown to be in part due to its up-regulation of the antiapoptotic protein Bcl-2 (13,14).…”

“…CD4 ϩ , CD45RA ϩ naive T cells, described as recent thymic emigrants (RTEs), 2 express a number of characteristics that distinguish them from naive T cells that are present later in life. They express high levels of the thymus-associated Ag CD38 and are characterized by decreased proliferative responses to Ag stimulation, decreased cytokine production, increased susceptibility to apoptosis and tolerance induction, as well as increased susceptibility to the immunosuppressive effects of cyclosporin A and glucocorticoids (1)(2)(3)(4)(5)(6)(7). RTEs exiting the thymus are preferentially incorporated into the periphery, causing displacement of resident mature T cells, thereby maintaining the size of the peripheral naive T cell pool (8) and ensuring that the TCR repertoire is kept diverse.…”

“…Uniquely, these RTEs proliferate in response to certain cytokines in the absence of Ag stimulation, unlike their adult-derived counterparts (6,9,10). These cytokines, which include IL-2, IL-4, and IL-7, play a vital role in the development, expansion, and survival of the lymphoid system (11).…”

Surface-engineering of lentiviral vectors

“…In this regard, IL7 is a promising candidate because: (1) it maintains the maturational state of T-cells [138] and (2) it promotes long-term T-cell survival in vitro [139]. Importantly, IL-7 does not switch T-cells to the memory phenotype [138,140] and triggers only a slight upregulation of activation markers in vitro [141].…”

GLUT-1 est le récepteur des rétrovirus humains HTLV

“…Or les lymphocytes T présents dans le sang de cordon, récents émigrants du thymus, présentent des caractéristiques d'activation distinctes de celles des cellules T périphériques de l'adulte. Une fois activées par l'IL-7, ces cellules, contrairement aux lymphocytes T de l'adulte [8,9], expriment le récepteur HTLV, les rendant ainsi théoriquement susceptibles à l'infection par HTLV [7]. Cette sensibilité à l'IL-7 des cellules T naïves pourrait ainsi expliquer la transmission préférentielle du virus HTLV de la mère infectée à l'enfant, même en l'absence de stimulation antigénique.…”