Opposite role for interleukin‐4 and interferon‐γ on CD30 and lymphocyte activation gene‐3 (LAG‐3) expression by activated naive T cells

Polarized human type 1 and type 2 T helper cells not only produce different sets of cytokines, but they also preferentially express certain activation markers, such as lymphocyte activation gene‐3 (LAG‐3) and CD30, respectively. In this study we have examined the LAG‐3 and CD30 expression in relation to the lineage commitment of human naive CD4+ T cells, as assessed at the single‐cell level of committed T cells. Purified CD45RA+ umbilical cord blood T lymphocytes were activated with phytohemagglutinin and interleukin (IL)‐2 in the absence or presence of interleukin IL‐4 or IL‐12 and assessed for CD30 and LAG‐3 expression, as well as for intracellular cytokine synthesis. Significant numbers of CD30+ cells were only found in CD4+ and CD8+ T lymphocytes of cultures primed with IL‐4, which developed into cells able to produce IL‐4 and IL‐13 in addition to interferon (IFN)‐γ. By contrast, LAG‐3 expression was strongly up‐regulated in CD4+ and CD8+ T cells from cultures primed with IL‐12, which developed into high numbers of IFN‐γ producers. The addition of a neutralizing anti‐IFN‐γ antibody to IL‐12‐primed CD4+ T cell cultures virtually abolished the development of LAG‐3‐expressing CD4+ T cells. Taken together, these data suggest that CD30 expression is dependent on the presence of IL‐4, whereas LAG‐3 expression is dependent on the production of IFN‐γ during the lineage commitment of human naive T cells.