Dendritic cell derived IL-12p70 stimulates IFN-γ production in naïve T cells, thereby promoting Th1 responses, which counteracts induction of tolerance. Uptake of apoptotic cells by dendritic cells is generally considered to induce tolerance rather than immune activation and has been shown to specifically inhibit IL-12 production. However, we previously demonstrated that the activation state of apoptotic PBMC influence their immunogenic potential. Here we investigated whether dendritic cells that have engulfed apoptotic PBMC are able to produce IL-12p70 after a secondary signal. We show that dendritic cell ability to produce IL-12p70 after uptake of allogeneic apoptotic cells is dependent on the activation state of the apoptotic cells and subsequent CD40 ligation. CD40 ligation by a CD40L-transfected cell-line induced IL-12p70 in DC regardless of previous apoptotic cell uptake. Moreover, dendritic cells that were exposed to allogeneic activated apoptotic PBMC, but not to resting apoptotic PBMC, were able to produce IL-12p70 after co-culture with autologous T cells. These findings show that dendritic cells are able to produce IL-12p70 upon engulfment of apoptotic cells provided that a secondary activating signal such as CD40-ligand is delivered. In addition, resting apoptotic cell but not activated apoptotic cells reduced ongoing IL-12p70 production suggesting that the balance of activated and resting apoptotic lymphocytes influence the amount of IL-12p70 being produced.
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