Abstract
γδ T cells are the first T cell lineage to develop in the thymus and take up residence in a wide variety of tissues where they can provide fast, innate-like sources of effector cytokines for barrier defense. In contrast to conventional αβ T cells that egress the thymus as naïve cells, γδ T cells can be programmed for effector function during development in the thymus. Understanding the molecular mechanisms that determine γδ T cell effector fate is of great interest due to the wide-spread tissue distribution of γδ T cells and their roles in pathogen clearance, immunosurveillance, cancer, and autoimmune diseases. In this review, we will integrate the current understanding of the role of the T cell receptor, environmental signals, and transcription factor networks in controlling mouse innate-like γδ T cell effector commitment.
Highlights
The DN3 stage represents an obligatory checkpoint at which productive rearrangement and expression of either a pre-T cell receptors (TCRs) (TCRβ + invariant pTα) or γδTCR complex signals the rescue of cells from apoptosis, proliferation, and αβ or γδ lineage differentiation [17]. β-selected cells undergo further development to the CD4+CD8+ double positive (DP) stage, where TCRα rearrangement and additional selection events yield mature CD4+ or CD8+ single positive αβ T cells [16, 20]
In contrast to αβ T cells that leave the thymus as naïve cells and acquire their effector function in the periphery, γδ T cells can commit to an effector fate during development in the thymus
While this review focuses on “pre-programmed” innate-like or “natural” γδ T cells, some γδ T cells exit the thymus as naïve cells and acquire effector function following activation in the periphery; these are referred to as “inducible” γδ T cells [4, 39]
Summary
Department of Immunology, Duke University Medical Center, Durham, NC, United States γδ T cells are the first T cell lineage to develop in the thymus and take up residence in a wide variety of tissues where they can provide fast, innate-like sources of effector cytokines for barrier defense. In contrast to conventional αβ T cells that egress the thymus as naïve cells, γδ T cells can be programmed for effector function during development in the thymus. Understanding the molecular mechanisms that determine γδ T cell effector fate is of great interest due to the wide-spread tissue distribution of γδ T cells and their roles in pathogen clearance, immunosurveillance, cancer, and autoimmune diseases. In this review, we will integrate the current understanding of the role of the T cell receptor, environmental signals, and transcription factor networks in controlling mouse innate-like γδ T cell effector commitment. Keywords: γδ T cells, thymus, TCR signal strength, transcriptional regulation, innate-like lymphocyte, IL-17A, IFNγ Reviewed by: Immo Prinz, Hannover Medical School, Germany Maria L. Toribio, Severo Ochoa Molecular Biology Center (CSIC-UAM), Spain Regulation of γδ T Cell Effector Diversification in the Thymus. Front. Immunol. 11:42.
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