title: Role of interferon-γ and cytotoxic T lymphocytes in intraocular tumor rejection.
abstract: The eye is normally an immunosuppressive environment. This condition is better known as immune privilege and protects the eye from immune-mediated inflammation of tissues that cannot regenerate. However, immune privilege creates a dilemma for the eye when intraocular neoplasms arise. In some cases, immune privilege is suspended, resulting in the immune rejection of intraocular tumors. This study employed a mouse model in which interferon-γ-dependent intraocular tumor rejection occurs. We tested the hypothesis that this rejection requires interferon-γ for the generation and functional capacity of cytotoxic T lymphocyte-mediated rejection of intraocular tumors. Tumors grew progressively in the eyes of interferon-γ knockout mice, even though the mice generated tumor-specific cytotoxic T lymphocyte responses in the periphery. However, interferon-γ knockout mice rejected tumors that were introduced into extraocular sites. Subcutaneous tumor immunization before intraocular challenge led to tumor rejection and preservation of the eye in wild-type mice. By contrast, tumors grew progressively in the eyes of interferon-γ knockout mice despite their ability to generate peripheral tumor-specific cytotoxic T lymphocytes as well as the capacity of CD8(+) T cells to enter the eye as shown by the presence of CD8 and perforin message and CD3(+)CD8(+) leukocytes within the tumor-bearing eye. We found that cytotoxic T lymphocytes generated in wild-type mice and adoptively transferred into interferon-γ knockout mice mediated the rejection of intraocular tumors in interferon-γ knockout hosts. The results indicate that interferon-γ is critical for the initial priming and differentiation of cytotoxic T lymphocytes residing in the periphery to produce the most effect antitumor function within the eye.
authors.affiliation: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, USA jerry.niederkorn@utsouthwestern.edu.
authors.forename: Ann J
authors.initials: AJ
authors.lastname: Ligocki
authors.affiliation: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Brown
authors.affiliation: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Jerry Y
authors.initials: JY
authors.lastname: Niederkorn
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D005134:Eye Neoplasms / Q000276:immunology* / Q000473:pathology*; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019007:P-Selectin / Q000378:metabolism; D054353:Perforin / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D017252:CD3 Complex; D015704:CD4 Antigens; D015815:Cell Adhesion Molecules; D019007:P-Selectin; D054353:Perforin; D007371:Interferon-gamma
keywords: CTL; IFN-γ; eye; immune privilege; necrotic inflammation