Stimulatory and inhibitory killer Ig-like receptor molecules are expressed and functional on lupus T cells.
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-gamma 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.
Basu
Dhiman
D
Department of Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Liu
Ying
Y
Wu
Ailing
A
Yarlagadda
Sushma
S
Gorelik
Gabriela J
GJ
Kaplan
Mariana J
MJ
Hewagama
Anura
A
Hinderer
Robert C
RC
Strickland
Faith M
FM
Richardson
Bruce C
BC
D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D054340:Receptors, KIR / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D054345:Receptors, KIR2DL4 / Q000502:physiology; D054341:Receptors, KIR3DL1 / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
D001324:Autoantigens; D003432:Cross-Linking Reagents; C515079:KIR2DL4 protein, human; C515083:KIR3DL1 protein, human; D054340:Receptors, KIR; D054345:Receptors, KIR2DL4; D054341:Receptors, KIR3DL1; D007371:Interferon-gamma
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