Regulation of γδ versus αβ T lymphocyte differentiation by the transcription factor SOX13

alpha beta and gamma delta T cells originate from a common, multipotential precursor population in the thymus, but the molecular mechanisms regulating this lineage-fate decision are unknown. We have identified Sox13 as a gamma delta-specific gene in the immune system. Using Sox13 transgenic mice, we showed that this transcription factor promotes gd T cell development while opposing ab T cell differentiation. Conversely, mice deficient in Sox13 expression exhibited impaired development of gd T cells but not ab T cells. One mechanism of SOX13 function is the inhibition of signaling by the developmentally important Wnt/T cell factor (TCF) pathway. Our data thus reveal a dominant pathway regulating the developmental fate of these two lineages of T lymphocytes.