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*
Dompé Research Center, L’Aquila, Italy;
Immunobiology and Cell Differentiation, Institute of Mutagenesis and Differentiation, National Research Council, Pisa, Italy; and
Pharmacology, Hannover Medical School, Hannover, Germany
MRL lpr/lpr mice spontaneously develop a
severe autoimmune lupus syndrome characterized by strong autoantibody
production and massive lymphoproliferation, in which IFN-
plays a
major pathogenic effect. The role of the IFN--inducing cytokine
IL-18 in the autoimmune syndrome of lpr/lpr mice has
been investigated. In response to IL-18, lymph node cells of
lpr/lpr mice produce significant amounts of IFN- and
proliferate more potently as compared with cells from +/+ mice. Cells
likely responsible for such hyperresponsiveness to IL-18 include NK
cells and the CD4+/CD8+ self-reactive T
lymphocytes characteristically present in lymph nodes of
lpr/lpr mice. Analysis of the expression of IL-18R
complex revealed that mRNA for the IL-18R
-chain is constitutively
expressed at similar level both in +/+ and lpr/lpr
lymphocytes. In contrast, the expression of the accessory receptor
chain IL-18R
is low in unstimulated +/+ cells but significantly high
in lpr/lpr cells. Thus, the abnormally high expression
of the IL-18R chain IL-18R could be one of the causes of the
hyperresponsiveness of lpr/lpr cells to IL-18 at the
basis of consequent enhancement of IFN- production and development
of IFN--dependent autoimmune pathology.
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