Recent insights into the signals that control αβ/γδ‐lineage fate

Abstract

During thymopoiesis, two major types of mature T cells are generated that can be distinguished by the clonotypic subunits contained within their T-cell receptor (TCR) complexes: alphabeta T cells and gammadelta T cells. Although there is no consensus as to the exact developmental stage where alphabeta and gammadelta T-cell lineages diverge, gammadelta T cells and precursors to the alphabeta T-cell lineage (bearing the pre-TCR) are thought to be derived from a common CD4- CD8- double-negative precursor. The role of the TCR in alphabeta/gammadelta lineage commitment has been controversial, in particular whether different TCR isotypes intrinsically favor adoption of the corresponding lineage. Recent evidence supports a signal strength model of lineage commitment, whereby stronger signals promote gammadelta development and weaker signals promote adoption of the alphabeta fate, irrespective of the TCR isotype from which the signals originate. Moreover, differences in the amplitude of activation of the extracellular signal-regulated kinase- mitogen-activated protein kinase-early growth response pathway appear to play a critical role. These findings will be placed in context of previous analyses in an effort to more precisely define the signals that control T-lineage fate during thymocyte development.