CD27 is a thymic determinant of the balance between interferon-γ- and interleukin 17–producing γδ T cell subsets

In peripheral lymphoid organs, γδ T cells are a source of interleukin 17. Silva-Santos and colleagues find that production of interleukin 17 versus interferon-γ by γδ T cells is inflexible and is determined in the thymus. The production of cytokines such as interferon-γ and interleukin 17 by αβ and γδ T cells influences the outcome of immune responses. Here we show that most γδ T lymphocytes expressed the tumor necrosis factor receptor family member CD27 and secreted interferon-γ, whereas interleukin 17 production was restricted to CD27− γδ T cells. In contrast to the apparent plasticity of αβ T cells, the cytokine profiles of these distinct γδ T cell subsets were essentially stable, even during infection. These phenotypes were established during thymic development, when CD27 functions as a regulator of the differentiation of γδ T cells at least in part by inducing expression of the lymphotoxin-β receptor and genes associated with trans-conditioning and interferon-γ production. Thus, the cytokine profiles of peripheral γδ T cells are predetermined mainly by a mechanism involving CD27.