New roles for IL-12: characterizing how IL-12 pretreatment alters human CD4 T cell responses (IRM5P.636)

Abstract

Abstract Antigen experienced CD4 T cells are constantly exposed to IL-12 during infections and autoimmune disorders. When given concurrently with TCR induction, IL-12 enhances IFN-γ production. However, alterations of TCR-mediated antigen experienced CD4 T cell functions by prior IL-12 exposure remain unexplored. To address this knowledge gap, human antigen experienced CD4 T cells were exposed to IL-12, IL-12 was then removed, and the cells were stimulated with anti-TCR antibodies. We found that IL-12 treatment increased TCR-induced IFN-γ, TNF-α, IL-13, IL-4 and IL-10 production in comparison to untreated cells. This suggests that prior exposure to IL-12 primes the TCR-induced release of a range of cytokines. The potentiation of TCR-mediated cytokine release required at least 90 minutes of IL-12 treatment and only lasted for 6-12 hours after IL-12 removal. Interestingly, we found that IL-12 exposure selectively increased the transcription of IFN-γ and IL-10 without altering the transcript levels of the other cytokines. Furthermore, IL-12 treatment increased the phosphorylation of AKT, p38 and LCK following TCR stimulation without altering other TCR signaling molecules. Our data uncover a new function of IL-12; IL-12 primes antigen experienced CD4 T cells to enhance cytokine release by “rewiring” TCR signaling pathways. This novel function of IL-12 provides insight into potential methods to enhance or suppress CD4 T cell activity that could be harnessed as therapeutics.