Bystander T cell activation: an immunologic double-edged sword

Memory CD8 T cells are conventionally called to arms by TCR recognition of cognate antigen; however, inflammation alone can elicit T cell cytotoxicity in the absence of cognate antigen. The consequences of this phenomenon, termed bystander activation, can range from beneficial (pathogen clearance) to deleterious (autoimmune pathology), yet the mechanisms controlling bystander-mediated cytotoxicity remain unclear. Here we demonstrate that bystander activation is immune to cell-intrinsic regulators of conventional T cell activation, given an independence to TCR signals. Instead, we show that bystander activation is shaped by cell-extrinsic factors, like IL-4 signals resulting from genetics, therapies, or contemporaneous infections. Lastly we demonstrate that conventional animal models underestimate the contribution of bystander activation to immunity. We explore the relevancy of these findings in sharpening protective bystander responses towards infections, blunting pathologic bystander responses, and harnessing this double-edged sword to destroy tumors.

Speaker: Nicholas Maurice, University of Minnesota