Inhibitor of DNA Binding 3 Limits Development of Murine Slam-Associated Adaptor Protein-Dependent Innate'' γδ T cells

Background: Id3 is a dominant antagonist of E protein transcription factor activity that is induced by signals emanating from the alpha beta and gamma delta T cell receptor (TCR). Mice lacking Id3 were previously shown to have subtle defects in positive and negative selection of TCR alpha beta(+) T lymphocytes. More recently, Id3(-/-) mice on a C57BL/6 background were shown to have a dramatic expansion of gamma delta T cells. Methodology/Principal Findings: Here we report that mice lacking Id3 have reduced thymocyte numbers but increased production of gamma delta T cells that express a V gamma 1.1(+)V delta 6.3(+) receptor with restricted junctional diversity. These V gamma 1.1(+)V delta 6.3(+) T cells have multiple characteristics associated with innate'' lymphocytes such as natural killer T (NKT) cells including an activated phenotype, expression of the transcription factor PLZF, and rapid production of IFNg and interleukin-4. Moreover, like other innate'' lymphocyte populations, development of Id3(-/-) V gamma 1.1(+)V delta 6.3(+) T cells requires the signaling adapter protein SAP. Conclusions: Our data provide novel insight into the requirements for development of V gamma 1.1(+)V delta 6.3(+) T cells and indicate a role for Id3 in repressing the response of innate'' gamma delta T cells to SAP-mediated expansion or survival.