Id3 Restricts the Developmental Potential of γδ Lineage during Thymopoiesis

Most T cell progenitors develop into the alpha beta T cell lineage with the exception of a small fraction contributing to the gamma delta lineage throughout postnatal life. T cell progenitors usually commit to the all lineage upon the expression of a fully rearranged and functional TCR beta gene, and most cells that fail to produce a functional TCR beta-chain will die instead of adopting the alternative gamma delta T cell fate. What prevents these cells from continuing TCR gamma rearrangement and adopting the gamma delta T cell fate is not known. In this study, we show that functional loss of Id3 results in a significant increase of gamma delta T cell production from progenitor cells undergoing TCR beta rearrangement. The enhanced gamma delta T cell development correlated with increased TCR gamma gene rearrangement involving primarily V gamma 1.1 in 10 deficient mice. We further show that Id3 deficiency promotes gamma delta T cell production in a manner independent of TCR beta-chain expression. Our data indicates that 10 suppresses V gamma 1.1 rearrangement and gamma delta lineage potential among T cell progenitors that have completed TCR beta gene rearrangement without producing a functional TCR beta protein. The Journal of Immunology, 2009, 182: 5306-5316.