Regulation of γδ T Cell Effector Diversification in the Thymus

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 widespread 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.

IL-4 and IL-17 Are Required for House Dust Mite-Driven Airway Hyperresponsiveness in Autoimmune Diabetes-Prone Non-Obese Diabetic Mice

“…The ability of remaining iNKT cells to produce high levels of IL-17 suggest that iNKT17 cells could contribute to airway inflammation, as described ( 18 ), and AHR observed in NOD mice. It is noteworthy that both iNKT and Vγ1 + T cells, in contrast to conventional CD4 + T cells, do not recognize peptides ( 33 – 35 ). These ILT cells can promptly produce cytokines following TCR-dependent or -independent activation ( 33 – 35 ).…”

Human γδ TCR Repertoires in Health and Disease

“…In mice, the development of several waves of γδ T cell subsets, such as Vγ5Vδ1 + dendritic epidermal T cells (DETCs) or Vγ6Vδ1 + IL-17-producing γδ T cells, exclusively takes place in the fetal thymus and these cells are maintained as long-lived effector cells after birth [23,24]. Early ontogenetic murine γδ T cell subsets are characterized by the expression of highly invariant and public TCRs that are shared among individual mice [55].…”

“…In contrast, Vγ7 + T cells reside as specialized intraepithelial lymphocytes in the gut, and Vγ1 + T cells circulate as naïve or IFN-γ-committed T cells in the periphery. Furthermore, IL-17-producing Vγ4 + or Vγ6 + T cells are enriched in tissues such as the dermis, oral mucosa, brain, joints or reproductive tracts [23,24]. Similarly, human γδ T cells can be roughly grouped by V-gene usage (Table 1).…”

A population of CD4+T cells with a naïve phenotype stably polarized to the TH1 lineage

“…The pattern of YFP positivity, marking cells that have experienced T-bet expression, recapitulates previous knowledge of T-bet function. For example, the expression of T-bet in developing NKT cells and γδ T cells in the thymus (58)(59)(60)(61). It has previously been reported that IFNγ-producing γδ T cells express T-bet and IL-17A producing γδ T cells express RORγt (60).…”