IL-6 trans-Signaling-Dependent Rapid Development of Cytotoxic CD8⁺ T Cell Function

Immune control of infections with viruses or intracellular bacteria relies on cytotoxic CD8⁺ Tcells that use granzyme B (GzmB) for elimination of infected cells. During inflammation, mature antigen-presenting dendritic cells instruct naive Tcells within lymphoid organs to develop into effector Tcells. Here, we report a mechanistically distinct and more rapid process of effector Tcell development occurring within 18hr. Such rapid acquisition of effector Tcell function occurred through cross-presenting liver sinusoidal endothelial cells (LSECs) in the absence of innate immune stimulation and known costimulatory signaling. Rather, interleukin-6 (IL-6) trans-signaling was required and sufficient for rapid induction of GzmB expression in CD8⁺ Tcells. Such LSEC-stimulated GzmB-expressing CD8⁺ Tcells further responded toinflammatory cytokines, eliciting increased and protracted effector functions. Our findings identify a role for IL-6 trans-signaling in rapid generation of effector function in CD8⁺ Tcells that may be beneficial for vaccination strategies.