γδ and αβ T cell lineage choice: Resolution by a stronger sense of being

A common bipotent thymocyte precursor gives rise to both lineages of T cells, alpha beta and gamma delta. However, the cell intrinsic and extrinsic factors that influence alpha beta-versus gamma delta-lineage bifurcation remain controversial. gamma delta T cells play a unique and vital role in host defense, from maintaining integrity at epithelial and mucosal barriers to their newly defined role as an important innate source of interleukin-17. Although a T cell receptor (TCR)-independent fate choice may take place, emerging data supports a model in which the differential signaling capacity of alpha beta and gamma delta TCRs play an instructional role in specifying lineage fate, with strength of signal measured by the amount of ERK/MAPK pathway activation. Here we discuss how the interplay between intrinsic TCR signals and cell extrinsic signals provided by Notch and TCR ligands help to assign and support a final lineage fate decision. (C) 2010 Elsevier Ltd. All rights reserved.