Gamma delta (γδ) T cells are a unique lineage of T cells distinguished by their T cell receptor (TCR), which consists of γ and δ chains. They exhibit distinct developmental and functional properties compared to conventional αβ T cells. While γδ T cells constitute a minor fraction of T cells in secondary lymphoid organs, they are enriched in epithelial tissues such as the epidermis and intestine. Studies in both mice and humans suggest that γδ T cells play protective and proinflammatory roles in infection, inflammation, and cancer. However, their non-redundant functions relative to αβ T cells remain less explored. Our previous work identified distinct γδ T cell subsets and their tissue residency across multiple organs in mice under steady-state conditions (du Halgouet et al., Nat Immunol 2024).
Using mouse models of bacterial (e.g., M. bovis) and viral (e.g., MCMV) infections, we now aim to decipher their functions using single-cell multiomics approaches. Additionally, by comparing their roles with αβ T cells, we seek to define γδ T cell–specific functions more precisely. Our preliminary results indicate distinct regulatory programs and differentiation states in γδ T cells compared to αβ T cells, particularly in pathways associated with macrophage differentiation and activation. Ongoing experiments aim to further elucidate the mechanisms driving these lineage-specific functions.
