Ocular immune privilege is circumvented by CD4+ T cells, leading to the rejection of intraocular tumors in an IFN-{gamma}-dependent manner.
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-gamma in the nonphthisical form of intraocular tumor rejection. The results showed that IFN-gamma induced tumor cell apoptosis, inhibited tumor cell proliferation, and promoted rejection by inhibiting angiogenesis. Microarray analysis revealed that IFN-gamma induced up-regulation of five antiangiogenic genes and down-regulation of four proangiogenic genes in Ad5E1 tumor cells. Although IFN-gamma knockout (KO) mice have progressively growing intraocular tumors, IFN-gamma was not needed for the elimination of extraocular tumors, as all IFN-gamma KO mice rejected s.c. tumor inocula. This represents a heretofore unrecognized role for IFN-gamma in circumventing ocular immune privilege and eliminating intraocular tumors. The findings also reveal that some IFN-gamma-independent tumor rejection processes are excluded from the eye and may represent a new facet of ocular immune privilege.
Dace
Dru S
DS
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9057, USA.
Chen
Peter W
PW
Alizadeh
Hassan
H
Niederkorn
Jerry Y
JY
D000818:Animals; D000867:Anterior Chamber / Q000187:drug effects / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005134:Eye Neoplasms / Q000276:immunology* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006084:Graft Rejection / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009368:Neoplasm Transplantation / Q000276:immunology; D009389:Neovascularization, Pathologic / Q000235:genetics; D001613:beta 2-Microglobulin / Q000276:immunology
D001613:beta 2-Microglobulin; D007371:Interferon-gamma