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

Autor: Jan P. Böttcher, Oliver Schanz, Christoph Garbers, Anne Zaremba, Silke Hegenbarth, Christian Kurts, Marc Beyer, Joachim L. Schultze, Wolfgang Kastenmüller, Stefan Rose-John, Percy A. Knolle
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: Cell Reports, Vol 8, Iss 5, Pp 1318-1327 (2014)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2014.07.008
Popis: Immune control of infections with viruses or intracellular bacteria relies on cytotoxic CD8+ T cells that use granzyme B (GzmB) for elimination of infected cells. During inflammation, mature antigen-presenting dendritic cells instruct naive T cells within lymphoid organs to develop into effector T cells. Here, we report a mechanistically distinct and more rapid process of effector T cell development occurring within 18 hr. Such rapid acquisition of effector T cell 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+ T cells. Such LSEC-stimulated GzmB-expressing CD8+ T cells further responded to inflammatory 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+ T cells that may be beneficial for vaccination strategies.
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