Development of all CD4 T lineages requires nuclear factor TOX (82.2)

Abstract

Abstract We have previously identified a nuclear factor member of the HMG-box superfamily, designated TOX, which is transiently expressed in the thymus during both positive selection and β-selection. We had shown that Tox is upregulated by calcineurin-dependent signaling and transgenic mice that express TOX generate CD8 single positive thymocytes (CD8SP), even in the absence of TCR signaling. We now report that mice deficient in TOX (TOX−/−) are outwardly normal but lack all CD4 lineage cells, namely CD4 αβ T, CD4 regulatory T and NK-T cells, due to a block in positive selection at the transitional CD4loCD8lo stage. In contrast, some CD8SP thymocytes develop in TOX−/− mice. These CD8SP can colonize the periphery and respond to TCR triggering. The block in CD4 T but not CD8 T cell development in TOX−/− mice is also observed in TCR transgenic animals. These results demonstrate differential requirements for the CD4 and CD8 lineages, where CD4-destined cells require induction of TOX for their development.