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Loss of TCR responsiveness during thymic education imprints the ‘innate’ signature on γδ T cells

Cellular & Molecular Immunology volume 11, pages 323–325 (2014)Cite this article

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T cells expressing γδ determinants are considered innate-like and deviate from the classical αβ T cells in many aspects, including the rapid production of lymphokines following the recognition of ‘naked’ antigens by the invariant T-cell receptor and failure to differentiate in the periphery. The details of thymic maturation in these atypical T cells have remained unclear. Recently, Wencker et al. demonstrated that during thymic education, γδ T cells acquire innate-like characteristics following the attrition of T-cell receptor (TCR)-mediated signaling.1 This previously unrecognized attribute could serve as a criterion for the subdivision of mature γδ T cells into subtypes.

The adaptive immune system, endowed with the unique ability to distinguish non-self from self and to retain memory for recall responses to a myriad of antigens, is a privilege of vertebrates, ranging from primitive jawless fish to mammals. The innate immune system is remarkably different from the adaptive immune system in these aspects and is highly conserved among the members of the plant and animal kingdoms. The ancient innate immune system has evolved various defense mechanisms under selective pressure in the form of bacterial and viral infections.2 In higher-order vertebrates, the innate immune system is represented by monocytes and their derivatives, such as dendritic cells. These cells are an integral part of the organized central and peripheral lymphoid tissues; they function as antigen presenting cells to the αβ T cells of the adaptive immune system. The complexity of αβ T cells for the most part has been revealed in the last 60 years. Recent years have witnessed the existence of a parallel universe of the adaptive immune system, uncovering at least three major types of innate lymphoid cells (ILCs) with distinguishable expression of transcription factors, similar to the CD4+ αβ T cells.3,4,5 Whereas the natural killer-like ILC1 cells express T-bet and produce IFN-γ, the Th2-like ILC2 cells are GATA-3+ and produce IL-4. The ILC3 cells are phenotypically heterogeneous and express various transcription factors. The lymphocytic inducer T cells colonize the gut-associated lymphoid patches early on during ontogeny and express T-bet. The NKp46+ ILC3 cell type expresses T-bet, IFN-γ, and as IL-22, cytokines that are considered characteristic of the Th17 subset. The Th17-like CCR6+ ILC3 cell type expresses RORγt, resulting in the transcription of IL-17A/F. In the face of this new knowledge about the ILCs, it is intriguing to consider whether a similar division of labor exists among the γδ T cells that assume a special niche in the immune system.

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  1. Department of Surgery, University of Illinois College of Medicine, Peoria, IL, USA

    Sundararajan Jayaraman

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  1. Sundararajan Jayaraman
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Correspondence to Sundararajan Jayaraman.

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Jayaraman, S. Loss of TCR responsiveness during thymic education imprints the ‘innate’ signature on γδ T cells. Cell Mol Immunol 11, 323–325 (2014). https://doi.org/10.1038/cmi.2014.10

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