Sage Journals: Discover world-class research

Abstract

Natural killer (NK) cells are important in the ocular surface innate response against viral and bacterial infection. Major-histocompatibility-complex class I-related chain A (MICA) antigens are ligands of natural killer group 2D, an activating or coactivating receptor expressed on NK cells. Recent studies demonstrated that interferon-gamma (IFN-γ) could modulate MICA expression in tumor cells. However, little is known about MICA expression and regulation in human corneal epithelium. Our study assessed whether the proinflammatory cytokine, IFN-γ, affects MICA expression in human corneal epithelium. We identified low levels of surface MICA expression in corneal epithelium using flow cytometry. IFN-γ promoted surface MICA expression in corneal epithelium and increased soluble MICA levels in a dose-dependent manner. IFN-γ also enhanced NK cell-mediated cytotoxicity against the corneal epithelium. Anti-MICA antibodies could further block this process. In summary, we describe a novel IFN-γ function in the regulation of the innate response in ocular surfaces.

Get full access to this article

View all access options for this article.

References

Bui

, Carayannopoulos

et al. 2006. IFN-dependent downregulation of the NKG2D ligand H60 on tumors. J Immunol, 176:905–913.

Cerwenka

, Lanier

. 2001. Natural killer cells, viruses and cancer. Nat Rev Immunol, 1:41–49.

Cerwenka

, Lanier

. 2003. NKG2D ligands: unconventional MHC class I-like molecules exploited by viruses and cancer. Tissue Antigen, 61:335–343.

Djalilian

, Namavari

et al. 2008. Down-regulation of Notch signaling during corneal epithelial proliferation. Mol Vis, 14:1041–1049.

Dong

, Zhang

et al. 2005. Impaired NK cell cytotoxicity by high level of interferon-γ in concanavalin A-induced hepatitis. Can J Physiol Pharmacol, 83:1045–1053.

González

, Groh

et al. 2006. Immunobiology of human NKG2D and its ligands. Curr Top Microbiol Immunol, 298:121–138.

Kim

, Chung

et al. 2007. Inhibitor of DNA binding 1 activates vascular endothelial growth factor through enhancing the stability and activity of hypoxia-inducible factor-1alpha. Mol Cancer Res, 5:321–329.

Maccalli

, Nonaka

et al. 2007. NKG2D-mediated antitumor activity by tumor-infiltrating lymphocytes and antigen-specific T-cell clones isolated from melanoma patients. Clin Cancer Res, 13:7459–7468.

Malmberg

, Levitsky

et al. 2002. IFN-γ protects short-term ovarian carcinoma cell lines from CTL lysis via a CD94/NKG2A-dependent mechanism. J Clin Invest, 110:1515–1523.

10.

Mistry

, O'Callaghan

. 2007. Regulation of ligands for the activating receptor NKG2D. Immunology, 121:439–447.

11.

Ota

, Takeda

et al. 2005. IFN-γ-mediated negative feedback regulation of NKT-cell function by CD94/NKG2. Blood, 106:184–192.

12.

Propper

, Chao

et al. 2003. Low-dose IFN-gamma induces tumor MHC expression in metastatic malignant melanoma. Clin Cancer Res, 9:84–92.

13.

Rager-Zisman

, Quan

et al. 1987. Role of NK cells in protection of mice against herpes simplex virus-1 infection. J Immunol, 138:884–888.

14.

Raulet

. 2003. Roles of the NKG2D immunoreceptor and its ligands. Nat Rev Immunol, 3:781–790.

15.

Saikali

, Antel

et al. 2007. NKG2D-mediated cytotoxicity toward oligodendrocytes suggests a mechanism for tissue injury in multiple sclerosis. J Neurosci, 27:1220–1228.

16.

Schwinn

, Vokhminova

et al. 2009. Interferon-gamma down-regulates NKG2D ligand expression and impairs the NKG2D-mediated cytolysis of MHC class I-deficient melanoma by natural killer cells. Int J Cancer, 124:1594–1604.

17.

Sundmacher

, Mattes

et al. 1987. The potency of interferon-alpha 2 and interferon-gamma in a combination therapy of dendritic keratitis. A controlled clinical study. Curr Eye Res, 6:273–276.

18.

Venkataraman

, Suciu

et al. 2007. Promoter region architecture and transcriptional regulation of the genes for the MHC class I-related chain A and B ligands of NKG2D. J Immunol, 178:961–969.

19.

, Chalupny

et al. 2003. Intracellular retention of the MHC class I-related chain B ligand of NKG2D by the human cytomegalovirus UL16 glycoprotein. J Immunol, 170:4196–4200.

20.

Zavazava

, Halene

et al. 1991. Expression of MHC class I and II molecules by cadaver retinal pigment epithelium cells: optimization of post-mortem HLA typing. Clin Exp Immunol, 84:163–166.

21.

Zhang

, Niu

et al. 2008. Opposing effects of interferon-alpha and interferon-gamma on the expression of major histocompatibility complex class I chain-related A in tumors. Cancer Sci, 99:1279–1286.

Interferon-γ Up-Regulates Major-Histocompatibility-Complex Class I-Related Chain A Expression and Enhances Major-Histocompatibility-Complex Class I-Related Chain A-Mediated Cytolysis of Human Corneal Epithelium by Natural Killer Cells In Vitro

Abstract

Get full access to this article

References