Activation of virus-specific CD8+ T cells by lipopolysaccharide-induced IL-12 and IL-18

Hans Peter Raué, James D. Brien, Erika Hammarlund, Mark K. Slifka

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

Virus-specific T cells represent a hallmark of Ag-specific, adaptive immunity. However, some T cells also demonstrate innate functions, including non-Ag-specific IFN-γ production in response to microbial products such as LPS or exposure to IL-12 and/or IL-18. In these studies we examined LPS-induced cytokine responses of CD8+ T cells directly ex vivo. Following acute viral infection, 70-80% of virus-specific T cells will produce IFN-γ after exposure to LPS-induced cytokines, and neutralization experiments indicate that this is mediated almost entirely through production of IL-12 and IL-18. Different combinations of these cytokines revealed that IL-12 decreases the threshold of T cell activation by IL-18, presenting a new perspective on IL-12/IL-18 synergy. Moreover, memory T cells demonstrate high IL-18R expression and respond effectively to the combination of IL-12 and IL-18, but cannot respond to IL-18 alone, even at high cytokine concentrations. This demonstrates that the synergy between IL-12 and IL-18 in triggering IFN-γ production by memory T cells is not simply due to up-regulation of the surface receptor for IL-18, as shown previously with naive T cells. Together, these studies indicate how virus-specific T cells are able to bridge the gap between innate and adaptive immunity during unrelated microbial infections, while attempting to protect the host from cytokine-induced immunopathology and endotoxic shock.

Original languageEnglish (US)
Pages (from-to)6873-6881
Number of pages9
JournalJournal of Immunology
Volume173
Issue number11
DOIs
StatePublished - Dec 1 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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