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Published online before print October 31, 2006

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(Journal of Leukocyte Biology. 2007;81:421-429.)
© 2007 by Society for Leukocyte Biology

Ocular immune privilege is circumvented by CD4⁺ T cells, leading to the rejection of intraocular tumors in an IFN--dependent manner

Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, USA

¹ Correspondence: Department of Ophthalmology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9057, USA. E-mail: jerry.niederkorn{at}utsouthwestern.edu

ABSTRACT

Although intraocular tumors reside in an immune-privileged site, they can circumvent immune privilege and undergo rejection, which typically follows one of two pathways. One pathway involves CD4⁺ T cells, delayed-type hypersensitivity (DTH), and the culmination in ischemic necrosis of the tumor and phthisis (atrophy) of the eye. The second pathway is DTH-independent and does not inflict collateral injury to ocular tissues, and the eye is preserved. In this study, we used a well-characterized tumor, Ad5E1, to analyze the role of IFN- in the nonphthisical form of intraocular tumor rejection. The results showed that IFN- induced tumor cell apoptosis, inhibited tumor cell proliferation, and promoted rejection by inhibiting angiogenesis. Microarray analysis revealed that IFN- induced up-regulation of five antiangiogenic genes and down-regulation of four proangiogenic genes in Ad5E1 tumor cells. Although IFN- knockout (KO) mice have progressively growing intraocular tumors, IFN- was not needed for the elimination of extraocular tumors, as all IFN- KO mice rejected s.c. tumor inocula. This represents a heretofore unrecognized role for IFN- in circumventing ocular immune privilege and eliminating intraocular tumors. The findings also reveal that some IFN--independent tumor rejection processes are excluded from the eye and may represent a new facet of ocular immune privilege.

Key Words: angiogenesis • anterior chamber

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