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Innate tissue immunosurveillance by γδ T cells has real-time dependence on the T cell receptor [ATAC-seq]

ABSTRACT: With clonotypic potential to engage different ligands, T cell receptor (TCR) γδ fulfils a key tenet of adaptive immunity. Nonetheless, many γδ repertoires are non-circulating, display limited diversity, and are commonly classified as innate-like, questioning any requirement for the TCR beyond the cells’ development. Addressing this long-standing issue, we now show that the steady-state phenotypes of different tissue-intrinsic γδ T cell compartments share a dependence on constitutive TCR expression. Deprived of this, cells rapidly become dysregulated, losing their capacity to respond to wide-ranging tissue insults, including imiquimod, an innate inducer of psoriasis-like pathology, u.v. irradiation, and melanoma. Thus, beyond any developmental requirements, the TCR is required in real time to regulate the cells’ innate-like tissue immunosurveillance. Biologically, this clearly distinguishes intrinsic γδ T cells from NK and other innate lymphoid cells, while clinically it stresses the importance of the TCR in delivering gd T cell-based immunotherapies.

ORGANISM(S): Mus musculus

PROVIDER: GSE277902 | GEO | 2026/01/21

REPOSITORIES: GEO

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Project description:γδ T cells are lymphocytes that function in both innate and adaptive immune responses, and our laboratory has previously reported that both bovine and human γδ T cells are primed for secondary responses by tannin components of the unripe apple peel (APP). In this report we began to investigate the mechanism by which priming occurs. We performed a microarray analysis on sorted bovine γδ T cells treated with APP and observed significant increases in transcripts encoding select inflammatory cytokines, such as GM-CSF, IL-8, and IL-17, but not markers of TCR stimulation such as IFNγ. When injected into the gut of mice, APP induced a robust influx of neutrophils into both the blood and peritoneum as measured by FACS. Importantly, both GM-CSF and IL-8 proteins were detected in these animals. Further studies were performed using the human γδ T cell-line MOLT-14, as large numbers of cells were required for subsequent experiments. Using these cells we found that both the GM-CSF and IL-8 mRNAs were significantly upregulated and stabilized in cells treated with APP. Finally, we show that the ERK1/2 MAPK pathway was activated in APP-treated MOLT-14 cells, and that this pathway plays a role in the mRNA stabilization we observed. Together, our data describe a unique inflammatory response in bovine, murine, and human γδ T cells in response to APP, and suggest that mRNA stability mechanisms could account for the priming phenotype we previously observed.APP has a distinctive gamma delta T cells specific priming activity. Keywords: comparison of 2 treatment types, tannin, gamma delta T cells To begin to understand the effects of APP in innate immunity, we investigated the global gene expression profiles of stimulated bovine gamma delta T cells. Peripheral blood from 2 neonatal bovine calves was collected. gamma delta T cells were sorted to >97% purity using a FACS Vantage. Cells were placed in culture and stimulated with either an aqueous extract of APP (42.2ug/ml) or PBS for 4 hours after which RNA was extracted and processed for microarray analysis following standard protocols from Affymetrix.

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Innate tissue immunosurveillance by γδ T cells has real-time dependence on the T cell receptor [ATAC-seq]

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