Exp Mol Med.  2009 Apr;41(4):288-295. 10.3858/emm.2009.41.4.032.

Nickel induces secretion of IFN-gamma by splenic natural killer cells

Affiliations
  • 1Division of Immunology, Department of Molecular Cell Biology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Korea. tjkim@skku.edu
  • 2Department of Dermatology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea.

Abstract

Although nickel hypersensitivity is known as a delayed-type hypersensitivity mediated by nickel-specific T cells, it is greatly influenced by other immune cells. Here we show that splenic natural killer cells (NK cells) directly or indirectly respond to nickel by secretion of IFN-gamma. Using enzyme-linked immunosorbent spot (ELISPOT) assays, we found that nickel-reactive cells readily secreted IFN-gamma when splenocytes were cultured in the presence of varying concentrations of nickel sulfate (NiSO4) for 24 h. However, nickel-reactive IL-2- or IL- 4-secreting cells were infrequent during the 24-h culture with NiSO4. Immune responses to nickel were innate, not adaptive, in nature since the frequency of nickel-reactive IFN-gamma-secreting cells did not increase upon previous exposure to NiSO4 and recombination activating gene (RAG)-1-deficient mice contained nickel-reactive IFN-gamma-secreting cells. The involvement of NK cells in the innate response to NiSO4 was confirmed since we could observe a significant reduction of the frequency of nickel-reactive cells in NK cell-depleted mice. Furthermore, the number of IFN-gamma secreting cells was significantly reduced in the ELISPOT assays when NKG2D was blocked by anti-NKG2D antibody. These results suggest that there is an early and rapid innate immune response to nickel, which is mediated by NK cells and the NKG2D receptor. The significance of the innate response to nickel is that it may contribute to development of the late T cell-mediated delayed type hypersensitivity against nickel.

Keyword

hypersensitivity; immunosorbent techniques; interferon-gamma; killer cells, natural; nickel; NK cell lectin-like receptor subfamily K

MeSH Terms

Animals
Homeodomain Proteins/genetics/metabolism
Humans
Immunity, Innate/immunology
Interferon-gamma/*secretion
*Irritants/immunology/pharmacology
*Killer Cells, Natural/drug effects/immunology/secretion
Mice
Mice, Inbred C57BL
Mice, Knockout
NK Cell Lectin-Like Receptor Subfamily K/genetics/metabolism
*Nickel/immunology/pharmacology
Spleen/*cytology/immunology
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