Diversification of Toxoplasma gondii-specific cytotoxic T lymphocytes by IL-12 (110.15)

Abstract The obligate intracellular parasite Toxoplasma gondii elicits a robust and uniquely IL-12 dependent CD8+ T cell immune response. We have previously shown that IL-12 is required for the differentiation of KLRG1+ CD8+ T effector cells following T. gondii infection. We have also shown that in the absence of IL-12, the frequency of KLRG1- memory precursor effector cell (MPECs) differentiation is increased at the expense of KLRG1+ short-lived effector cells (SLECs). Therefore, IL-12 may be a critical signal for the early phase bifurcation of naïve CD8+ T cells into KLRG1+ SLEC and KLRG1- MPEC-fated lymphocytes. To determine if SLECs and MPECs are generated in the earliest phase of CD8+ T cell activation, we enumerated T. gondii reactive CD8+ T cells by magnetic bead enrichment of Kb-tgd057 tetramer binding cells. We have found that the initial proliferation of tgd057-specific CD8+ T cells in the spleen occurs between day 3 and day 5 following T. gondii infection. Concurrently, KLRG1+ and KLRG1- CD8+ T cells can be observed in both the spleen and the effector site of the peritoneum, suggesting early diversification of tgd057-specific CD8+ T cells. Current efforts are geared towards visualizing the events leading to the initial bifurcation of the CD8+ T cell response and determining how IL-12 regulates this decision-making process.