Id3 restricts the developmental potential of gamma delta lineage during thymopoiesis.
Most T cell progenitors develop into the alphabeta T cell lineage with the exception of a small fraction contributing to the gammadelta lineage throughout postnatal life. T cell progenitors usually commit to the alphabeta lineage upon the expression of a fully rearranged and functional TCRbeta gene, and most cells that fail to produce a functional TCRbeta-chain will die instead of adopting the alternative gammadelta T cell fate. What prevents these cells from continuing TCRgamma rearrangement and adopting the gammadelta T cell fate is not known. In this study, we show that functional loss of Id3 results in a significant increase of gammadelta T cell production from progenitor cells undergoing TCRbeta rearrangement. The enhanced gammadelta T cell development correlated with increased TCRgamma gene rearrangement involving primarily Vgamma1.1 in Id3 deficient mice. We further show that Id3 deficiency promotes gammadelta T cell production in a manner independent of TCRbeta-chain expression. Our data indicates that Id3 suppresses Vgamma1.1 rearrangement and gammadelta lineage potential among T cell progenitors that have completed TCRbeta gene rearrangement without producing a functional TCRbeta protein.
Ueda-Hayakawa
Ikuko
I
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Mahlios
Josh
J
Zhuang
Yuan
Y
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D055786:Gene Knockout Techniques; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor / Q000235:genetics; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / Q000235:genetics; D051796:Inhibitor of Differentiation Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D051796:Inhibitor of Differentiation Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; C067679:Idb3 protein, mouse