Expansion of human γδ T cells in periphery: Lessons learned from development, infections, and compromised thymic function

γδ T cells predominantly develop in the fetal period. Post birth they respond swiftly to environmental insults, pathogens and tumors, especially when other immune effector cells are less ready to function. Most of our understanding of γδ T-cell development, peripheral adaptation, and function derives from murine studies. The recent advancement of immunological methods allows now to decipher human γδ T-cell biology in patient cohorts and tissue samples, and to manipulate them using in vitro systems. In this review, we summarize γδ T-cell development in the human thymus, their functional adaptation to the microbial environment from birth until old age, and their capacity to expand and fill up the peripheral niche under conditions of perturbations of conventional T-cell development.