γδ Thymocyte Maturation and Emigration in Adult Mice

Abstract

Several unique waves of γδ T cells are generated solely in the fetal/neonatal thymus, whereas additional γδ T cell subsets are generated in adults. One intriguing feature of γδ T cell development is the coordination of differentiation and acquisition of effector function within the fetal thymus; however, it is less clear whether this paradigm holds true in adult animals. In this study, we investigated the relationship between maturation and thymic export of adult-derived γδ thymocytes in mice. In the Rag2pGFP model, immature (CD24+) γδ thymocytes expressed high levels of GFP whereas only a minority of mature (CD24−) γδ thymocytes were GFP+. Similarly, most peripheral GFP+ γδ T cells were immature. Analysis of γδ recent thymic emigrants (RTEs) indicated that most γδ T cell RTEs were CD24+ and GFP+, and adoptive transfer experiments demonstrated that immature γδ thymocytes can mature outside the thymus. Mature γδ T cells largely did not recirculate to the thymus from the periphery; rather, a population of mature γδ thymocytes that produced IFN-γ or IL-17 remained resident in the thymus for at least 60 d. These data support the existence of two populations of γδ T cell RTEs in adult mice: a majority subset that is immature and matures in the periphery after thymic emigration, and a minority subset that completes maturation within the thymus prior to emigration. Additionally, we identified a heterogeneous population of resident γδ thymocytes of unknown functional importance. Collectively, these data shed light on the generation of the γδ T cell compartment in adult mice.

The medulla controls effector primed γδT‐cell development in the adult mouse thymus

“…The ability to study regulation of Τ‐cell development in adult mice requires direct identification of immature thymocytes undergoing de novo intrathymic development. This is of particular significance for study of effector γδT‐cell development, as recent findings show the adult thymus contains subsets of mature, IL17, and IFN‐γ‐producing γδT cells that represent long‐term thymus residents [ 6 ]. Consistent with this, analysis of γδT‐cell development in adult Rag2GFP reporter mice, where the presence and amount of GFP identifies the relative age of different thymocyte populations [ 8 ], identified a dominant GFP + γδ thymocyte population that represents cells undergoing development, and an additional smaller population of GFP − cells that represents mature γδT cells (Fig.…”

“…This is perhaps at least in part due to the complexity of the adult intrathymic γδT‐cell pool. For example, recent studies show this population is developmentally heterogeneous, consisting of a mixture of immature γδ thymocytes that represent de novo γδT‐cell development, and fully mature γδT‐cells that have completed their maturation and not undergone thymic export, and so represent long‐term thymus‐resident cells [ 6 ]. As such, understanding the regulation of γδ thymocyte development in the adult thymus, including intrathymic effector priming, is hindered by a lack of approaches to accurately define and study stages in de novo effector γδT‐cell development.…”

Intrathymic somatotropic circuitry: consequences upon thymus involution

“…Some γδ T cells emigrate from the thymus while still immature, but others complete their maturation within the organ before migrating to the periphery. Mature γδ T cells possess a defined effector profile (associated with interferon-gamma (IFN-γ) or IL-17 production) and can play several roles in the immune system like as protection against tumors and infections ( 67 , 68 ).…”

Dietary glucosamine overcomes the defects in αβ-T cell ontogeny caused by the loss of de novo hexosamine biosynthesis

“…In contrast, weaker signals skew development towards the αβ-T cell lineage. Whereas αβ-T cells, which undergo extensive thymic selection, exit the thymus in a naïve state and acquire effector functions in the periphery, γδ-T cells can become endowed with effector functions in the thymus and subsequently populate the epithelium and mucosa-associated lymphoid tissues 2,[12][13][14] . How metabolism influences lineage fates in the thymus by impacting the expression of cell surface receptors, as well as associated intracellular signals, remains to be further explored.…”