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This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0900034v1 183/5/3481    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Basu, D. Articles by Richardson, B. C. PubMed PubMed Citation Articles by Basu, D. Articles by Richardson, B. C.

Stimulatory and Inhibitory Killer Ig-Like Receptor Molecules Are Expressed and Functional on Lupus T Cells¹

Dhiman Basu^*, Ying Liu^*, Ailing Wu^*, Sushma Yarlagadda^*, Gabriela J. Gorelik^*, Mariana J. Kaplan^*, Anura Hewagama^*, Robert C. Hinderer^*, Faith M. Strickland^* and Bruce C. Richardson^2,*,

^* Department of Medicine, University of Michigan, Ann Arbor, MI 48109; and Ann Arbor Veterans Affairs Medical Center, Ann Arbor, MI 48105

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- 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 costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Public Health Service Grants AR42525, AR56370, AG25877, and ES15214, National Institute on Aging Training Grant AG000114, and a Merit Grant from the Veterans Administration.

² Address correspondence and reprint requests to Dr. Bruce Richardson, Department of Medicine, University of Michigan, 3007 Biomedical Science Research Building (BSRB), Ann Arbor, MI 48109. E-mail address: brichard{at}umich.edu

³ Abbreviations used in this paper: M, macrophage; KIR, killer cell Ig-like receptor; SLE, systemic lupus erythematosus; SLEDAI, systemic lupus erythematosus disease activity index; MS-PCR, methylation-sensitive PCR; 5-azaC, 5-azacytidine.