USE OF IL-12 TO ALTER EPIGENETIC EFFECTOR PROGRAMS IN CD8 T CELLS

摘要

Provided herein are methods and compositions for modulating T-cell activity by incubating a CD8 T cell with a signal 3 cytokine, such as IL-12. Incubation of naïve CD8 T cells, particularly, with a signal 3 cytokine can acquire long-lived memory associated gene expression characteristic of the stem cell memory subset of CD8 T cells. Further, incubation with signal 3 cytokines can induce changes to the epigenetic profile of naïve CD8 T cells that are more characteristic of bona fide Tscmcells than in vitro generated cells using traditional differentiation protocols. On account of epigenetic profiles being preserved during in vivo homeostasis, signal 3 cytokines such as IL-12 can be used to engineer a T cell population with the desired epigenetic profile that maintains effector functions and proliferative capacity.