Role Of Interferon-Gamma And Cytotoxic T Lymphocytes In Intraocular Tumor Rejection
JOURNAL OF LEUKOCYTE BIOLOGY(2016)
摘要
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-gamma-dependent intraocular tumor rejection occurs. We tested the hypothesis that this rejection requires interferon-gamma for the generation and functional capacity of cytotoxic T lymphocyte-mediated rejection of intraocular tumors. Tumors grew progressively in the eyes of interferon-gamma knockout mice, even though the mice generated tumor-specific cytotoxic T lymphocyte responses in the periphery. However, interferon-gamma 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-gamma 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-gamma knockout mice mediated the rejection of intraocular tumors in interferon-gamma knockout hosts. The results indicate that interferon-gamma 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.
更多查看译文
关键词
eye, immune privilege, necrotic inflammation, CTL, IFN-gamma
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要