Inhibitor of DNA binding 3 limits development of murine slam-associated adaptor protein-dependent "innate" γδ T cells

Abstract

Background: Id3 is a dominant antagonist of E protein transcription factor activity that is induced by signals emanating from the αβ and γδ T cell receptor (TCR). Mice lacking Id3 were previously shown to have subtle defects in positive and negative selection of TCRαβ + T lymphocytes. More recently, Id3-/- mice on a C57BL/6 background were shown to have a dramatic expansion of γδ T cells. Methodology/Principal Findings: Here we report that mice lacking Id3 have reduced thymocyte numbers but increased production of γδ T cells that express a Vγ1.1+Vd6.3+ receptor with restricted junctional diversity. These Vγ1.1+Vδ6.3+ 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-/- Vγ1.1+Vδ6.3 + T cells requires the signaling adapter protein SAP. Conclusions: Our data provide novel insight into the requirements for development of Vγ1.1+Vδ6.3+ T cells and indicate a role for Id3 in repressing the response of "innate" γδ T cells to SAP-mediated expansion or survival. © 2010 Verykokakis et al.