To Be γδ or Not to Be γδ? Signaling Pathways in αβ Versus γδ T Cell Maturation

Maturation of T cells in the thymus involves input from a number of signaling pathways; their combined input determines whether thymic precursor cells will differentiate into mature alpha beta or gamma delta T cells. This Journal Club article highlights recent research showing that the role of Notch signaling in human T cell maturation differs from that in mice. In mice, reducing Notch gene dosage in vivo promotes gamma delta T cell differentiation. In humans, an increase in Notch activity early in development will trigger gamma delta T cell development. This research emphasizes how the molecular events controlling T cell development are fundamentally different in humans and mice.