Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12

A novel sequence discovered in a computational screen appears distantly rel ated to the p35 subunit of IL-12. This factor, which we term p19, shows no biological activity by itself; instead, it combines with the p40 subunit of IL-12 to form a novel, biologically active, composite cytokine, which we t erm IL-23. Activated dendritic cells secrete detectable levels of this comp lex. IL-23 binds to IL-12R beta1 but fails to engage IL-12R beta2; nonethel ess, IL-23 activates Stat4 in PHA blast T cells. IL-23 induces strong proli feration of mouse memory (CD4(+)CD45Rb(low))T cells, a unique activity of I L-23 as IL-12 has no effect on this cell population. Similar to IL-12, huma n IL-23 stimulates IFN-gamma production and proliferation in PHA blast T ce lls, as well as in CD45RO (memory)T cells.