γδ cells:: A right time and a right place for a conserved third way of protection

The tripartite subdivision of lymphocytes into B cells, alpha beta T cells, and gamma delta cells has been conserved seemingly since the emergence of jawed vertebrates, more than 450 million years ago. Yet, while we understand much about B cells and alpha beta T cells, we lack a compelling explanation for the evolutionary conservation of gamma delta cells. Such an explanation may soon be forthcoming as advances in unraveling the biochemistry of gamma delta cell interactions are reconciled with the abnormal phenotypes of gamma delta-deficient mice and with the striking differences in gamma delta cell activities in different strains and species. In this review, the properties of gamma delta cells form a basis for understanding gamma delta cell interactions with antigens and other cells that in turn form a basis for understanding immunoprotective and regulatory functions of gamma delta cells in vivo. We conclude by considering which gamma delta cell functions may be most critical.