Rejection of intraocular tumors by CD4+ T cells without induction of phthisis
Rejection of intraocular tumors by CD4+ T cells without induction of phthisis
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DOI：
10.4049/jimmunol.167.10.5832
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发表时间：
2001-11-15
影响因子：
4.4
通讯作者：
Toes, REM
中科院分区：
文献类型：
--
作者：
Schurmans, LRHM;Diehl, L;Toes, REM
眼睛的免疫赦免可防止威胁视力的炎症事件，但也可能允许原本不致命的免疫原性肿瘤生长。然而，眼部肿瘤的生长可受细胞免疫反应控制。但是，如果肿瘤排斥是由CD4(+) T细胞介导的迟发型超敏反应所调控，通常会导致眼球萎缩。我们现在表明，CD4(+)辅助性T细胞可根除眼内肿瘤，而不会对邻近的眼部组织造成附带损伤。将由人腺病毒5型早期区域I转化的肿瘤细胞注射到眼前房会导致眼内肿瘤形成。在免疫功能正常的小鼠中肿瘤生长是暂时的，但在免疫缺陷的裸鼠中是致命的，这表明依赖T细胞的免疫负责肿瘤清除。肿瘤排斥具有CD8(+) T细胞介导的免疫反应的所有特征，因为肿瘤不表达MHC II类分子，且只有肿瘤组织受到破坏。然而，对参与肿瘤清除的分子和细胞机制的分析表明，穿孔素、TNF -α、Fas配体、MHC I类分子和CD8(+) T细胞在肿瘤根除中没有起到关键作用。相反，有效的肿瘤排斥完全依赖于CD4(+)辅助性T细胞，因为去除CD4以及MHC II类分子缺陷的小鼠无法排斥其眼内肿瘤。综上所述，这些观察结果表明，CD4(+) T细胞能够在免疫赦免部位根除MHC II类阴性肿瘤，而不影响周围组织或诱发眼球萎缩。
Immune privilege of the eye protects against sight-threatening inflammatory events, but can also permit outgrowth of otherwise nonlethal immunogenic tumors. Nonetheless, ocular tumor growth can be controlled by cellular immune responses. However, this will normally result in phthisis of the eye, in case tumor rejection is mediated by a delayed-type hypersensitivity response orchestrated by CD4(+) T cells. We now show that intraocular tumors can be eradicated by CD4(+) Th cells without inducing collateral damage of neighboring ocular tissue. Injection of tumor cells transformed by the early region I of human adenovirus type 5 in the anterior chamber of the eye leads to intraocular tumor formation. Tumor growth is transient in immunocompetent mice, but lethal in immunodeficient nude mice, indicating that T cell-dependent immunity is responsible for tumor clearance. Tumor rejection has all the characteristics of a CD8(+) T cell-mediated immune response, as the tumor did not express MHC class II and only tumor tissue was the subject of destruction. However, analysis of the molecular and cellular mechanisms involved in tumor clearance revealed that perforin, TNF-alpha, Fas ligand, MHC class I, and CD8(+) T cells did not play a crucial role in tumor eradication. Instead, effective tumor rejection was entirely dependent on CD4(+) Th cells, as CD4-depleted as well as MHC class II-deficient mice were unable to reject their intraocular tumor. Taken together, these observations demonstrate that CD4(+) T cells are able to eradicate MHC class U-negative tumors in an immune-privileged site without affecting surrounding tissues or the induction of phthisis.