(A)- To initiate IL-12p75 production during cognate interactions, DCs must first receive at least three signals: (1) CD40L, (2) IL-4 and (3) GM-CSF. Although, during the TDC interactions engagement of TCR/MHC will lead to IFN-γ production independent of IL-12p75, its presence is dispensable during the initiation of IL-12p75 production. (B) Once IL-12p75 is produced it will act on competent T cells that express functional IL-12 receptors (IL-12Rß1 & ß2), which will increase the level of IFN-γ that was already being produced as the result of TCR/MHC engagements. (C) The formation of a positive feedback loop created by IL-12→ IFN-γ will ensure their amplification, which leads to sustain IFN-γ–mediated immune responses. However, eventually, subsequent negative feedback (not shown) will inhibit the expansion of this loop.