Stimulatory and inhibitory killer Ig-like receptor molecules are expressed and functional on lupus T cells. Other Scholarly Work

Basu, Dhiman, Liu, Ying, Wu, Ailing et al. (2009). Stimulatory and inhibitory killer Ig-like receptor molecules are expressed and functional on lupus T cells. . Journal of Immunology, 183(5), 3481-3487. 10.4049/jimmunol.0900034

cited authors

  • Basu, Dhiman; Liu, Ying; Wu, Ailing; Yarlagadda, Sushma; Gorelik, Gabriela J; Kaplan, Mariana J; Hewagama, Anura; Hinderer, Robert C; Strickland, Faith M; Richardson, Bruce C

authors

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-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.

publication date

  • September 1, 2009

published in

keywords

  • Autoantigens
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Cross-Linking Reagents
  • Cytotoxicity Tests, Immunologic
  • DNA Methylation
  • Female
  • Humans
  • Interferon-gamma
  • Lupus Erythematosus, Systemic
  • Macrophages
  • Male
  • Receptors, KIR
  • Receptors, KIR2DL4
  • Receptors, KIR3DL1
  • T-Lymphocyte Subsets

Location

  • England

Digital Object Identifier (DOI)

start page

  • 3481

end page

  • 3487

volume

  • 183

issue

  • 5