OPPOSITE ROLE FOR INTERLEUKIN-4 AND INTERFERON-GAMMA 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 diff erent sets of cytokines, but they also preferentially express certain activation markers, such as lymphocyte activation gene-3 (LAG-3) and C D30, respectively. In this study we have examined the LAG-3 and CD30 e xpression in relation to the lineage commitment of human naive CD4(+) T cells, as assessed at the single-cell level of committed T cells. Pu rified CD45RA(+) umbilical cord blood T lymphocytes were activated wit h phytohemagglutinin and interleukin (IL)-2 in the absence or presence of interleukin IL-4 or IL-12 and assessed for CD30 and LAG-3 expressi on, as well as for intracellular cytokine synthesis. Significant numbe rs of CD30(+) cells were only found in CD4(+) and CD8(+) T Iymphocytes of cultures primed with IL-4, which developed into cells able to prod uce IL-4 and IL-13 in addition to interferon (IFN)-gamma. By contrast, LAG-3 expression was strongly up-regulated in CD4(+) and CD8(+) T cel ls from cultures primed with IL-12, which developed into high numbers of IFN-gamma producers. The addition of a neutralizing anti-IFN-gamma antibody to IL-12-primed CD4(+) T cell cultures virtually abolished th e development of LAG-3-expressing CD4(+) T cells. Taken together, thes e data suggest that CD30 expression is dependent on the presence of IL -4, whereas LAG-3 expression is dependent on the production of IFN-gam ma during the lineage commitment of human naive T cells.