Maintenance of immune tolerance depends on normal tissue homeostasis
Maintenance of immune tolerance depends on normal tissue homeostasis
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DOI：
10.4049/jimmunol.175.7.4247
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发表时间：
2005-10-01
影响因子：
4.4
通讯作者：
Toes, REM
中科院分区：
文献类型：
--
作者：
Boonman, ZFHM;van Mierlo, GJD;Toes, REM
在免疫特权部位和其他外周组织表达的Ags能够诱导T细胞耐受。在这项研究中，我们分析了在眼睛解剖完整性丧失的情况下，对表达高度免疫原性CTL表位的眼内肿瘤的耐受性是否维持、破坏或恢复为免疫。将肿瘤细胞接种到初生B6小鼠的眼前房，导致眼内肿瘤的进行性生长，在肿瘤引流的下颌下淋巴结中CTL激活的流产形式，以及这些小鼠无法拒绝原本良性的肿瘤细胞接种的系统性耐受性。由于肺结核导致的眼睛解剖完整性的丧失导致了全身耐受性的丧失和对致命肿瘤攻击的有效抗肿瘤免疫的出现。肺结核伴随着树突状细胞的成熟，并先于系统性肿瘤特异性CTL免疫的诱导。我们的数据表明，正常组织稳态和解剖完整性是维持眼耐受性和预防ctl介导的免疫所必需的。这些数据还表明，在没有病毒或微生物感染的情况下，组织损伤可以作为诱导CTL免疫的开关。
Ags expressed at immune privileged sites and other peripheral tissues are able to induce T cell tolerance. In this study, we analyzed whether tolerance toward an intraocular tumor expressing a highly immunogenic CTL epitope is maintained, broken, or reverted into immunity in the event the anatomical integrity of the eye is lost. Inoculation of tumor cells into the anterior chamber of the eye of naive B6 mice leads to progressive intraocular tumor growth, an abortive form of CTL activation in the tumor-draining submandibular lymph node, and systemic tolerance as evidenced by the inability of these mice to reject an otherwise benign tumor cell inoculum. Loss of anatomical integrity of the eye as a consequence of phthisis resulted in loss of systemic tolerance and the emergence of effective antitumor immunity against an otherwise lethal tumor challenge. Phthisis was accompanied by dendritic cell maturation and preceded the induction of systemic tumor-specific CTL immunity. Our data show that normal tissue homeostasis and anatomical integrity is required for the maintenance of ocular tolerance and prevention of CTL-mediated immunity. These data also indicate that tissue injury in the absence of viral or microbial infection can act as a switch for the induction of CTL immunity.