Stimulatory and Inhibitory Killer Ig-Like Receptor Molecules Are Expressed and Functional on Lupus T Cells
Copyright policy )Stimulatory and Inhibitory Killer Ig-Like Receptor Molecules Are Expressed and Functional on Lupus T Cells
Abstract T cells from lupus patients have hypomethylated DNA and overexpress genes normally suppressed by DNA methylation that contribute to disease pathogenesis. We found that stimulatory and inhibitory killer cell Ig-like receptor (KIR) genes are aberrantly overexpressed on experimentally demethylated T cells. We therefore asked if lupus T cells also overexpress KIR, and if the proteins are functional. T cells from lupus patients were found to overexpress KIR genes, and expression was proportional to disease activity. Abs to the stimulatory molecule KIR2DL4 triggered IFN-γ release by lupus T cells, and production was proportional to disease activity. Similarly, cross-linking the inhibitory molecule KIR3DL1 prevented the autoreactive macrophage killing that characterizes lupus T cells. These results indicate that aberrant T cell KIR expression may contribute to IFN overproduction and macrophage killing in human lupus, and they suggest that Abs to inhibitory KIR may be a treatment for this disease.
- University of Michigan–Flint United States
- University of Michigan–Ann Arbor United States
CD4-Positive T-Lymphocytes, Male, Macrophages, Receptors, KIR3DL1, CD8-Positive T-Lymphocytes, DNA Methylation, Cytotoxicity Tests, Immunologic, Autoantigens, Interferon-gamma, Cross-Linking Reagents, Receptors, KIR, Receptors, KIR2DL4, T-Lymphocyte Subsets, Humans, Lupus Erythematosus, Systemic, Female
CD4-Positive T-Lymphocytes, Male, Macrophages, Receptors, KIR3DL1, CD8-Positive T-Lymphocytes, DNA Methylation, Cytotoxicity Tests, Immunologic, Autoantigens, Interferon-gamma, Cross-Linking Reagents, Receptors, KIR, Receptors, KIR2DL4, T-Lymphocyte Subsets, Humans, Lupus Erythematosus, Systemic, Female
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