Visualization of the earliest steps of γδ T cell development in the adult thymus

Abstract

The checkpoint in gammadelta cell development that controls successful T cell receptor (TCR) gene rearrangements remains poorly characterized. Using mice expressing a reporter gene 'knocked into' the Tcrd constant region gene, we have characterized many of the events that mark the life of early gammadelta cells in the adult thymus. We identify the developmental stage during which the Tcrd locus 'opens' in early T cell progenitors and show that a single checkpoint controls gammadelta cell development during the penultimate CD4- CD8- stage. Passage through this checkpoint required the assembly of gammadelta TCR heterodimers on the cell surface and signaling via the Lat adaptor protein. In addition, we show that gammadelta selection triggered a phase of sustained proliferation similar to that induced by the pre-TCR.