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

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-gamma 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-gamma 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-gamma 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.

• Authors: Hans-Peter Raué, James D Brien, Erika Hammarlund, Mark K Slifka
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 173 Issue 11 Pg. 6873-81 (Dec 01 2004) ISSN: 0022-1767 [Print] United States
• PMID: 15557182 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Epitopes, T-Lymphocyte
• Il18r1 protein, mouse
• Interleukin-18
• Interleukin-18 Receptor alpha Subunit
• Lipopolysaccharides
• Protein Subunits
• Receptors, Interleukin
• Receptors, Interleukin-18
• Interleukin-12
• Interferon-gamma

Topics

• Animals
• CD8-Positive T-Lymphocytes (cytology, immunology, metabolism, virology)
• Cell Differentiation (immunology)
• Cells, Cultured
• Down-Regulation (immunology)
• Drug Synergism
• Epitopes, T-Lymphocyte (immunology)
• Immunity, Innate
• Interferon-gamma (biosynthesis)
• Interleukin-12 (biosynthesis, physiology)
• Interleukin-18 (antagonists & inhibitors, biosynthesis, metabolism, physiology)
• Interleukin-18 Receptor alpha Subunit
• Kinetics
• Lipopolysaccharides (pharmacology)
• Lymphocyte Activation (immunology)
• Lymphocytic choriomeningitis virus (immunology)
• Mice
• Mice, Inbred BALB C
• Protein Subunits (biosynthesis, physiology)
• Receptors, Interleukin (biosynthesis, physiology)
• Receptors, Interleukin-18
• Shock, Septic (immunology)
• Up-Regulation (immunology)