Persistence of physiological self antigen is required for the regulation of self tolerance
Persistence of physiological self antigen is required for the regulation of self tolerance
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DOI：
10.4049/jimmunol.164.8.3982
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发表时间：
2000-04-15
影响因子：
4.4
通讯作者：
Tung, KSK
中科院分区：
文献类型：
--
作者：
Garza, KM;Agersborg, SS;Tung, KSK
在表达转基因抗原和/或其同源转基因TCR的小鼠中，已广泛研究了诱导和维持T细胞耐受性的内源性Ag需求，而对生理表达的自身抗原和正常T细胞的耐受性研究较少。在这里，我们证明了小鼠卵巢特异的ZP3抗原从出生就可以检测到。雌性小鼠对ZP3的耐受性高于雄性小鼠。与男性相比，女性需要100倍以上的卵巢多肽(PZP3)才能引起类似的致病反应，女性对pZP3的耐受性取决于内源性卵巢抗原的存在，因为新生儿卵巢切除将女性的反应转换为男性的反应。此外，在1-6周龄去卵巢的雌性小鼠中，如果在成年前用pZP3攻击前7天而不是3天摘除卵巢，pZP3的反应就会增强到雄性水平。因此，生理表达的ZP3Ag诱导了对pZP3的耐受，耐受的维持依赖于内源性卵巢抗原的持续存在，相反，仅限于新生期的内源性卵巢抗原的暴露不足以诱导和维持对ZP3的耐受。
Endogenous Ag requirement for induction and maintenance of T cell tolerance has been extensively investigated in mice that express a transgenic Ag and/or its cognate transgenic TCR, In contrast, studies on tolerance for physiologically expressed self Ag and normal T cells are limited. Herein, we showed that the murine ovarian-specific ZP3 Ag is detectable from birth. Tolerance to ZP3 is detected in female relative to male mice. In comparison to males, 100-fold more ovarian peptide (pZP3) is required to elicit a comparable pathogenic response in females, Female tolerance to pZP3 was dependent on the presence of endogenous ovarian Ag, because neonatal ovariectomy converted the female response to that of males. Moreover, in female mice that were ovariectomized from the ages of 1-6 wk, the pZP3 responses were enhanced to the male level if ovaries were removed up to 7 days, but not 3 days, before adult challenge with pZP3. Thus, the physiologically expressed ZP3 Ag induces tolerance to pZP3, and the maintenance of tolerance is critically dependent on the continuous presence of the endogenous ovarian Ag, In contrast, exposure to endogenous ovarian Ag confined to the neonatal period is insufficient for the induction and maintenance of tolerance to ZP3.