Stimulatory and Inhibitory Killer Ig-Like Receptor Molecules Are Expressed and Functional on Lupus T Cells

被引：51

作者：

Basu, Dhiman ^{[1
]}

Liu, Ying ^{[1
]}

Wu, Ailing ^{[1
]}

Yarlagadda, Sushma ^{[1
]}

Gorelik, Gabriela J. ^{[1
]}

Kaplan, Mariana J. ^{[1
]}

Hewagama, Anura ^{[1
]}

Hinderer, Robert C. ^{[1
]}

Strickland, Faith M. ^{[1
]}

Richardson, Bruce C. ^{[1
,2
]}

机构：

[1] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA

[2] Ann Arbor Vet Affairs Med Ctr, Ann Arbor, MI 48105 USA

来源：

JOURNAL OF IMMUNOLOGY | 2009年 / 183卷 / 05期

关键词：

IMMUNOGLOBULIN-LIKE RECEPTORS; DRUG-INDUCED LUPUS; DNA METHYLATION; MONONUCLEAR-CELLS; KIR; DEMETHYLATION; OVEREXPRESSION; 5-AZACYTIDINE; DISEASE; LYMPHOCYTES;

D O I：

10.4049/jimmunol.0900034

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

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. The Journal of Immunology, 2009, 183: 3481-3487.

引用

页码：3481 / 3487

页数：7

共 38 条

[1]

DERIVATION OF THE SLEDAI - A DISEASE-ACTIVITY INDEX FOR LUPUS PATIENTS [J].