Human fetal γδ T cells seed developing organs with transient tissue-specific immunity

However, the fate and role of these distinct thymic effector populations remain unknown. Therefore, we performed a cross-organ single-cell multi-omics study integrating gene expression, paired TCR and surface protein profiles across the human fetal γδ T cell compartment of lymphoid organs (blood, spleen, lymph nodes), liver and barrier tissues (lung, intestine, skin) during mid-gestation.

Fetal tissues are dominated by Vδ2+ γδ T cells which are organized into organ-specific effector subsets associated with tissue-residence status and public γδ TCR clonotypes. Integration with existing databases showed that type 2-like and type 3 functional programs, together with their public clonotypes, are highly restricted to the fetal period, indicating a transient, developmentally tailored wave. These findings reveal that the human fetus harbors unique organ-associated γδ T cell programs and provide a reference framework for understanding immune responses in early human life.