Cutting edge:: TLR ligands are not sufficient to break cross-tolerance to self-antigens
Cutting edge:: TLR ligands are not sufficient to break cross-tolerance to self-antigens
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DOI：
10.4049/jimmunol.174.3.1159
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发表时间：
2005-02-01
影响因子：
4.4
通讯作者：
Kurts, C
中科院分区：
文献类型：
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作者：
Hamilton-Williams, EE;Lang, A;Kurts, C
树突状细胞（DC）交叉呈递外周自身抗原可通过交叉耐受机制诱导自身反应性CTL的缺失。微生物TLR配体激活DC被认为导致获得性免疫。然而，致耐受性DC的活化可能通过刺激而不是删除自身反应性CTL而引起自身免疫。为了研究这种情况下，我们已经监测了特异性的转基因自身抗原，OVA，表达的RIP-mOVA小鼠的胰岛注射TLR 2，3，4，和9的配体的自身反应性CTL的反应。这在一定程度上增强了增殖和细胞因子的产生，并适度减少了能够诱导自身免疫的CTL数量。然而，除非提供，否则生理CTL数目在疾病发生之前被删除。总之，在缺乏特异性CD 4 T细胞辅助的情况下，TLR配体对DC特异性CD 4 T细胞辅助的激活不足以打破外周交叉耐受，并且仅在自身反应性CTL的前体频率极高时才通过刺激自身反应性CTL的早期效应相来触发自身免疫。
Cross-presentation of peripheral self-Ags by dendritic cells (DC) can induce deletion of autoreactive CTL by a mechanism termed cross-tolerance. Activation of DC by microbial TLR ligands is thought to result in adaptive immunity. However, activation of tolerogenic DC may cause autoimmunity by stimulating instead of deleting autoreactive CTL. To investigate this scenario, we have monitored the response of autoreactive CTL in specific for the transgenic self Ag, OVA, expressed in pancreatic islets of RIP-mOVA mice injected with ligands of TLR2, 3, 4, and 9. This somewhat enhanced proliferation and cytokine production, and moderately reduced the CTL number able to induce autoimmunity. Nevertheless, physiological CTL numbers were deleted before disease ensued, unless was provided. In conclusion, DC specific CD4 T cell help activation by TLR ligands was insufficient to break peripheral cross-tolerance in the absence of specific CD4 T cell help, and triggered autoimmunity by stimulating the early effector phase of autoreactive CTL only when their precursor frequency was extremely high.