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Gammadelta T cells (γδ T cells) are T cells that express a unique T-cell receptor (TCR) composed of one γ-chain and one δ-chain. Gammadelta T cells are of low abundance in the body, are found in the gut mucosa, skin, lungs and uterus, and are involved in the initiation and propagation of immune responses.
Immune checkpoint blockade cancer therapy has been designed to enable tumor killing by conventional αβ T cells. Here authors show that in a Merkel cell carcinoma patient showing complete response to anti-PD-1 treatment, innate-like γδ T cells that specifically recognize the tumor cells expand, and likely contribute to therapeutic success.
γδ T cells are known to recognize phosphoantigen in the context of butyrophilins (BTN), yet the molecular rules underlying this phenomenon are unclear. Here, the authors demonstrate that a distinct topology of B30.2 and IgV domains within BTN3A complexes promotes antigen sensing and that the juxtamembrane region controls BTN complex formation.
γδ T cells are unique T lymphocytes with cytotoxic functions, targeting infections and tumours. Here authors show that the target killing function of γδ T cells is tightly regulated at the level of the availability of lytic molecules granzyme B and perforin.
A combination of genome-wide CRISPR screens in target cancer cells identifies pathways that regulate γδ T cell killing and BTN3A cell surface expression.
Traumatic brain injury is not only a neurological but also an immunological condition in which multiple innate and adaptive immune cell types play roles. Here authors show in a mouse model that the Vγ4 subtype of the unconventional gamma-delta T cells promote neuroinflammation, while the Vγ1 subtype ameliorates immunopathology.
Kamiya and colleagues examine the effects of chronic social-defeat stress on the intestinal microbiome and show a pathological role played by dectin-1 and interleukin-17 expressed by gut γδ T cells on this behavioral vulnerability.
On 20–23 June 2023, the 10th International γδ T cell conference was held in Lisbon, Portugal, bringing together basic, translational and clinical researchers studying γδ T cells in health and disease.
A study in Immunity reports that a high-fat diet in mice leads to the loss of PPARγ+ Treg cells in the skin, which exacerbates psoriasis mediated by IL-17-producing γδ T cells.
Chronic stress in mice induces microbial dysbiosis and affects the differentiation of γδ T cells in the colon. These cells accumulate in the meninges and cause depression-like behaviour, which can be reversed by targeting the pattern recognition receptor dectin-1.
Although the aryl hydrocarbon receptor has an essential role in supporting homeostasis of intestinal intraepithelial lymphocytes, its activation must be regulated to prevent oxidative stress and death of these cells.