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Published online before print October 31, 2006

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0806489

Received for publication August 1, 2006.
Revised September 12, 2006.
Accepted for publication September 29, 2006.

Article

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

^@ To whom correspondence should be addressed. 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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				D. S. Dace, P. W. Chen, and J. Y. Niederkorn CD8+ T Cells Circumvent Immune Privilege in the Eye and Mediate Intraocular Tumor Rejection by a TNF-{alpha}-Dependent Mechanism J. Immunol., May 15, 2007; 178(10): 6115 - 6122. [Abstract] [Full Text] [PDF]