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

The production of cytokines such as interferon-gamma and interleukin 17 by alpha beta and gamma delta T cells influences the outcome of immune responses. Here we show that most gamma delta T lymphocytes expressed the tumor necrosis factor receptor family member CD27 and secreted interferon-gamma, whereas interleukin 17 production was restricted to CD27(-) gamma delta T cells. In contrast to the apparent plasticity of gamma delta T cells, the cytokine profiles of these distinct alpha beta 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 gamma delta T cells at least in part by inducing expression of the lymphotoxin-beta receptor and genes associated with trans-conditioning and interferon-gamma production. Thus, the cytokine profiles of peripheral gamma delta T cells are predetermined mainly by a mechanism involving CD27.