The Journal of Immunology, Vol 156, Issue 8 2667-2673, Copyright © 1996 by American Association of Immunologists

ARTICLES

Isolation and characterization of a unique natural killer cell inhibitory factor present in the anterior chamber of the eye

RS Apte and JY Niederkorn
Graduate Program in Immunology, University of Texas Southwestern Medical Center, Dallas 75235, USA.

The eye is a classic example of an immunologically privileged organ. Immune privilege in the anterior chamber is a multifaceted phenomenon that may have evolved to protect delicate ocular tissues from immune- mediated damage. The anterior chamber of the eye is lined with corneal endothelial cells, which are terminally differentiated cells that are incapable of regeneration. Since corneal endothelial cells are crucial for maintaining corneal clarity, damage to these cells leads to impairment of vision and, in some cases, blindness. The absence of constitutive expression of MHC class I molecules on corneal endothelial cells makes them potential targets for NK cell-mediated cytolysis. The aqueous humor (AH) that fills the anterior chamber of the eye and bathes the corneal endothelial surface contains numerous immunomodulatory molecules, such as TGF-beta, which may protect the corneal endothelium from NK cell-mediated damage. Functionally significant levels of TGF-beta are present in AH. In this study, we demonstrate that AH inhibits NK cell-mediated cytotoxicity in vitro, but does not affect cytotoxic T lymphocyte-mediated lysis. The inhibitory effect was immediate and occurred without preincubation of NK cells with aqueous humor. The inhibitory factor could not be neutralized by Abs to TGF-beta, but was abrogated by treating AH with proteases. Inhibition was not simply due to lysis of NK cells, since AH did not alter NK cell viability. Initial purification using gel filtration chromatography showed that the activity was restricted to a single elution peak. Analysis of the active fractions by gel electrophoresis indicated that the inhibitory factor was a single protein of approximately 10 kilodaltons. The NK inhibitory factor might be an important modulator for protecting the corneal endothelium from unbridled NK cell-mediated injury and, thus, might be instrumental in preserving vision.

This article has been cited by other articles:

				Y. Futagami, S. Sugita, J. Vega, K. Ishida, H. Takase, K. Maruyama, H. Aburatani, and M. Mochizuki Role of Thrombospondin-1 in T Cell Response to Ocular Pigment Epithelial Cells J. Immunol., June 1, 2007; 178(11): 6994 - 7005. [Abstract] [Full Text] [PDF]

				H. Alizadeh, K. Howard, J. Mellon, E. Mayhew, D. Rusciano, and J. Y. Niederkorn Reduction of Liver Metastasis of Intraocular Melanoma by Interferon-{beta} Gene Transfer Invest. Ophthalmol. Vis. Sci., July 1, 2003; 44(7): 3042 - 3051. [Abstract] [Full Text] [PDF]

				M. E. Skelsey, J. Mellon, and J. Y. Niederkorn {{gamma}}{{delta}}T Cells Are Needed for Ocular Immune Privilege and Corneal Graft Survival J. Immunol., April 1, 2001; 166(7): 4327 - 4333. [Abstract] [Full Text] [PDF]

				S. Sugita, C. Taguchi, H. Takase, K. Sagawa, J. Sueda, K. Fukushi, N. Hikita, T. Watanabe, K. Itoh, and M. Mochizuki Soluble Fas ligand and soluble Fas in ocular fluid of patients with uveitis Br. J. Ophthalmol., October 1, 2000; 84(10): 1130 - 1134. [Abstract] [Full Text]

				A. C. Repp, E. S. Mayhew, S. Apte, and J. Y. Niederkorn Human Uveal Melanoma Cells Produce Macrophage Migration-Inhibitory Factor to Prevent Lysis by NK Cells J. Immunol., July 15, 2000; 165(2): 710 - 715. [Abstract] [Full Text] [PDF]

				M. Tanigawa, J. E. Bigger, M. Y. Kanter, and S. S. Atherton Natural Killer Cells Prevent Direct Anterior-to-Posterior Spread of Herpes Simplex Virus Type 1 in the Eye Invest. Ophthalmol. Vis. Sci., January 1, 2000; 41(1): 132 - 137. [Abstract] [Full Text]

				E. Mavoungou, A. Sall, V. Poaty-Mavoungou, F. S. Toure, P. Yaba, A. Delicat, and J. Lansoud-Soukate Alloreactivity and Association of Human Natural Killer Cells with the Major Histocompatibility Complex Clin. Vaccine Immunol., March 1, 1999; 6(2): 254 - 259. [Abstract] [Full Text] [PDF]

				K. Lingnau, P. Hoehn, S. Kerdine, S. Koelsch, C. Neudoerfl, N. Palm, E. Ruede, and E. Schmitt IL-4 in Combination with TGF-{beta} Favors an Alternative Pathway of Th1 Development Independent of IL-12 J. Immunol., November 1, 1998; 161(9): 4709 - 4718. [Abstract] [Full Text] [PDF]

				R. S. Apte, D. Sinha, E. Mayhew, G. J. Wistow, and J. Y. Niederkorn Cutting Edge: Role of Macrophage Migration Inhibitory Factor in Inhibiting NK Cell Activity and Preserving Immune Privilege J. Immunol., June 15, 1998; 160(12): 5693 - 5696. [Abstract] [Full Text] [PDF]

				J. E. Bigger, C. A. Thomas III, and S. S. Atherton NK Cell Modulation of Murine Cytomegalovirus Retinitis J. Immunol., June 15, 1998; 160(12): 5826 - 5831. [Abstract] [Full Text] [PDF]