TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand

We recently showed that dendritic cells ( DCs) activated by thymic stromal lymphopoietin ( TSLP) prime naive CD4(+) T cells to differentiate into T helper type 2 ( Th2) cells that produced high amounts of tumor necrosis factor-alpha ( TNF-alpha), but no interleukin ( IL)-10. Here we report that TSLP induced human DCs to express OX40 ligand ( OX40L) but not IL-12. TSLP-induced OX40L on DCs was required for triggering naive CD4(+) T cells to produce IL-4, -5, and -13. We further revealed the following three novel functional properties of OX40L: ( a) OX40L selectively promoted TNF-alpha, but inhibited IL-10 production in developing Th2 cells; ( b) OX40L lost the ability to polarize Th2 cells in the presence of IL-12; and ( c) OX40L exacerbated IL-12-induced Th1 cell inflammation by promoting TNF-alpha, while inhibiting IL-10. We conclude that OX40L on TSLP- activated DCs triggers Th2 cell polarization in the absence of IL-12, and propose that OX40L can switch IL-10-producing regulatory Th cell responses into TNF-alpha-producing inflammatory Th cell responses.