Perinatal γδ T cells: between invariance and diversity

The perinatal period represents a unique immunological window of opportunity, in which γδ T cells play a central role. New methods, including single-cell and high-resolution TCR repertoire analyses, have transformed our understanding of how γδ T cells develop, diversify, and function from fetal life into adulthood. Early γδ T cell waves display TCRs shaped by low TdT activity, biased V(D)J recombination, and favored V-J and V-D pairings that give rise to public, near germline-encoded TCRs with preprogrammed effector functions. These fetal-derived populations contribute to rapid pathogen responses and unique pathogen-driven expansions during congenital infections, revealing fundamental differences between perinatal and adult γδ T cell immunity. However, it is less clear how pre- and perinatal γδ T cells persist and influence individual immune responses later in life. This review synthesizes current insights into ontogeny, effector programming, and repertoire dynamics of γδ T cells in early life. We focus on deciphering the evident changes in the γδ T cell compartment during gestation, birth, and early life in humans.