Perinatal γδ T cells: between invariance and diversity

Area of Science:

• Immunology
• Developmental Biology
• T Cell Biology

Background:

• The perinatal period is a critical immunological window where gamma delta (γδ) T cells are central players.
• Recent advancements in single-cell and T-cell receptor (TCR) repertoire analyses have significantly advanced our understanding of γδ T cell development and function.
• Distinctive features of fetal-derived γδ T cells suggest unique roles in early-life immunity compared to adult responses.

Purpose of the Study:

• To review current knowledge on the ontogeny, effector programming, and repertoire dynamics of γδ T cells during early human development.
• To elucidate the changes in the γδ T cell compartment throughout gestation, birth, and early infancy.
• To understand the long-term influence of perinatal γδ T cells on individual immune responses.

Main Methods:

• Synthesis of current research findings on γδ T cell development and function.
• Analysis of data from single-cell and high-resolution TCR repertoire studies.
• Focus on human studies detailing changes during gestation, birth, and early life.

Main Results:

• Early γδ T cells possess TCRs shaped by specific V(D)J recombination, resulting in public, germline-encoded TCRs with pre-programmed effector functions.
• Fetal-derived γδ T cells mediate rapid responses to pathogens and exhibit unique expansions during congenital infections.
• Significant differences exist between perinatal and adult γδ T cell immunity, though the persistence and long-term impact of perinatal populations require further investigation.

Conclusions:

• γδ T cells undergo distinct developmental trajectories and functional programming during the perinatal period.
• These early-life γδ T cells play a crucial role in innate-like immune responses and may shape long-term immunity.
• Further research is needed to fully comprehend the persistence and influence of perinatal γδ T cells on lifelong immune health.