FIGURE 8.
Engagement of TIM-3 by Ab during Ag stimulation of CD8 T cells activates mTORC1 to drive differentiation into effector cells. CD8 T cells responding to Ag-specific stimulation in vitro act as predicted by proliferating and increasing cytokine production, and they exhibit target killing in a typical cytotoxicity assay. The known ligands, Gal9, HMGB1, and PtdS, are all likely present in that they are widely expressed by many different cell types including T cells, yet the mTOR pathway is not uniformly activated so there is a higher frequency of cells representing TEM compared with TEFF (left). Addition of anti–TIM-3 Ab during Ag stimulation results in specific activation of mTORC1 shown by increased pS6 and RhebL1 expression and ultimately the frequency of TEFF is increased (right).