The γδ T Cell Club: bringing a global scientific community together in the age of Zoom.

Immunologists are very social people-they love to meet other immunologists and talk about immunology (and immunologists). Constantly! γδ T-cell researchers are no exception. On the contrary, as there are not so many of them compared to, say, researchers working on dendritic cells, they especially crave frequent interactions with like-minded scientists.

Mouse genome rewriting and tailoring of three important disease loci.

Genetically engineered mouse models (GEMMs) help us to understand human pathologies and develop new therapies, yet faithfully recapitulating human diseases in mice is challenging. Advances in genomics have highlighted the importance of non-coding regulatory genome sequences, which control spatiotemporal gene expression patterns and splicing in many human diseases. Including regulatory extensive genomic regions, which requires large-scale genome engineering, should enhance the quality of disease modelling.

Helminth resistance is mediated by differential activation of recruited monocyte-derived alveolar macrophages and arginine depletion.

Macrophages are known to mediate anti-helminth responses, but it remains uncertain which subsets are involved or how macrophages actually kill helminths. Here, we show rapid monocyte recruitment to the lung after infection with the nematode parasite Nippostrongylus brasiliensis. In this inflamed tissue microenvironment, these monocytes differentiate into an alveolar macrophage (AM)-like phenotype, expressing both SiglecF and CD11c, surround invading parasitic larvae, and preferentially kill parasites in vitro.

Transcriptional programming and gene regulation in WC1 γδ T cell subpopulations.

γδ T cells represent a high proportion of lymphocytes in the blood of ruminants with the majority expressing lineage-specific glycoproteins from the WC1 family. WC1 receptors are coded for by a multigenic array whose genes have variegated but stable expression among cells in the γδ T cell population. WC1 molecules function as hybrid pattern recognition receptors as well as co-receptors for the TCR and are required for responses by the cells.

Beyond neutralization for BNT162b2 mRNA vaccination.

Mounting a robust immune response against SARS-CoV-2 requires neutralization as well as effector T cell functions. In this issue of Cell Host Microbe, Tauzin et al. characterize the humoral and T cell responses after a single dose of BNT162b2 mRNA vaccine in individuals with or without previous exposure to SARS-CoV-2.

Special features of γδ T cells in ruminants.

Ruminant γδ T cells were discovered in the mid-1980's shortly after a novel T cell receptor (TCR) gene from murine cells was described in 1984 and the murine TCRγ gene locus in 1985. It was possible to identify γδ T cell populations early in ruminants because they represent a large proportion of the peripheral blood mononuclear cells (PBMC). This null cell population, γδ T cells, was designated as such by its non-reactivity with monoclonal antibodies (mAb) against ovine and bovine CD4, CD8 and surface immunoglobulin (Ig).

Gene characterization and expression of the γδ T cell co-receptor WC1 in sheep.

Sheep are known to express the hybrid co-receptor/pattern recognition receptor WC1 on their γδ T cells but details of the ovine WC1 multigenic array and gene expression were unknown. Annotation of the sheep genome assembly (Oar_rambouillet_v1.0) yielded 15 complete and 42 partial WC1 genes predicted to code for six different protein structures.

Identification of a nerve-associated, lung-resident interstitial macrophage subset with distinct localization and immunoregulatory properties.

Tissue-resident macrophages are a diverse population of cells that perform specialized functions including sustaining tissue homeostasis and tissue surveillance. Here, we report an interstitial subset of CD169 lung-resident macrophages that are transcriptionally and developmentally distinct from alveolar macrophages (AMs). They are primarily localized around the airways and are found in close proximity to the sympathetic nerves in the bronchovascular bundle.

γδ T cells in livestock: Responses to pathogens and vaccine potential.

The immediate objective of our research is to understand the molecular mechanisms underlying activation and potentiation of the protective functional response of WC1 γδ T cells to pathogens afflicting livestock species. The long-term goal is to incorporate stimulation of these cells into the next generation of vaccine constructs. γδ T cells have roles in the immune response to many infectious diseases including viral, bacterial, protozoan and worm infections, and their functional responses overlap with those of canonical αβ T cells, for example they produce cytokines including interferon-γ and IL-17.

Bovine T cell receptors and γδ WC1 co-receptor transcriptome analysis during the first month of life.

Here we evaluated neonatal transcription of α, β, γ and δ TCR and the γδ T cell co-receptor family WC1 in peripheral blood mononuclear cells. A previous report showed a rapid and global shift in transcription of immunoglobulin genes in neonatal calves during the first month after birth but this was not found here for the T cell genes. Transcription frequency of genes within TRAV subgroups correlated with the number of members, indicating a stochastic choice.

Variegated Transcription of the WC1 Hybrid PRR/Co-Receptor Genes by Individual γδ T Cells and Correlation With Pathogen Responsiveness.

γδ T cells have broad reactivity and actively participate in protective immunity against tumors and infectious disease-causing organisms. In γδ-high species such as ruminants and other artiodactyls many γδ T cells bear the lineage-specific markers known as WC1. WC1 molecules are scavenger receptors coded for by a multigenic array and are closely related to SCART found on murine γδ T cells and CD163 found on a variety of cells.