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

Kieran D James, Andrea J White, William E Jenkinson, Graham Anderson*

*Corresponding author for this work

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Abstract

γδT cells are produced in the thymus throughout life and provide immunity at epithelial-rich sites. Unlike conventional αβT cells, γδT-cell development involves intrathymic acquisition of effector function, with priming for either IL17 or IFN-γ production occurring during embryonic or adult life, respectively. How the thymus controls effector-primed γδT-cell generation in adulthood is poorly understood. Here, we distinguished de novo γδT cells from those undergoing thymus recirculation and/or retention using Rag2GFP mice alongside markers of maturation/effector priming including CD24, CD25, CD73, and IFN-γ, the latter by crossing with IFN-γYFP GREAT mice. We categorize newly developing γδT-cells into an ordered sequence where CD25+ CD73- IFN-γYFP- precursors are followed sequentially by CD25- CD73+ IFN-γYFP- intermediates and CD25- CD73+ IFN-γYFP+ effectors. To determine intrathymic requirements controlling this sequence, we examined γδT-cell development in Relb-/- thymus grafts that lack medullary microenvironments. Interestingly, medulla deficiency did not alter CD25+ γδT-cell precursor generation, but significantly impaired development of effector primed stages. This impact on γδT-cell priming was mirrored in plt/plt mice lacking the medullary chemoattractants CCL19 and CCL21, and also Ccl21a-/- but not Ccl19-/- mice. Collectively, we identify the medulla as an important site for effector priming during adult γδT-cell development and demonstrate a specific role for the medullary epithelial product CCL21 in this process.

Original languageEnglish
Article numbere2350388
JournalEuropean Journal of Immunology
Volume53
Issue number6
Early online date16 Mar 2023
DOIs
Publication statusPublished - 6 Jun 2023

Bibliographical note

© 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.

Keywords

  • Animals
  • Mice
  • Thymus Gland
  • Cell Differentiation
  • Interferon-gamma
  • Receptors, Antigen, T-Cell, gamma-delta/genetics

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