Miller J F, Kurts C, Allison J, Kosaka H, Carbone F, Heath W R
Walter and Eliza Hall Institute of Medical Research, P.O. Royal Melbourne Hospital, Victoria, Australia.
Immunol Rev. 1998 Oct;165:267-77. doi: 10.1111/j.1600-065x.1998.tb01244.x.
There is now convincing evidence that CD8+ T cells can be activated by professional antigen-presenting cells which present antigens derived from non-lymphoid tissues in association with MHC class I molecules in the draining lymph nodes. This mechanism, referred to as cross-presentation, enables the immune system to respond to those microorganisms that infect only non-lymphoid tissues. Consistent with this view, cross-presentation was found to focus on antigens expressed in high concentrations and those released from dying cells, which can be expected to result from viral infections. Recent evidence, however, demonstrates that high dose self antigens can be cross-presented constitutively, resulting in the activation of autoreactive CD8+ T cells. This does not lead to auto immunity under physiologic conditions, but to CD95-mediated deletion of the T cells. Cross-presentation can thus engage a well-defined pathway of antigen-induced T-cell death and purge the immune system of autoreactive CD8+ T cells. Low dose self antigens are not cross-presented and are consequently ignored. The immune system therefore uses two strategies to avoid CD8+ T-cell-mediated autoimmunity in the periphery: deletion of autoreactive CD8+ T cells responding to high dose self antigens and ignorance of self antigens expressed at low concentrations.
目前有确凿证据表明，CD8 + T细胞可被专职抗原呈递细胞激活，这些细胞在引流淋巴结中呈递源自非淋巴组织的抗原，并与MHC I类分子结合。这种机制被称为交叉呈递，它使免疫系统能够对那些仅感染非淋巴组织的微生物做出反应。与此观点一致的是，交叉呈递被发现集中于高浓度表达的抗原以及垂死细胞释放的抗原，这些抗原可能是由病毒感染产生的。然而，最近的证据表明，高剂量自身抗原可被组成性地交叉呈递，从而导致自身反应性CD8 + T细胞的激活。在生理条件下，这不会导致自身免疫，而是导致CD95介导的T细胞缺失。因此，交叉呈递可以启动一条明确的抗原诱导的T细胞死亡途径，并清除免疫系统中的自身反应性CD8 + T细胞。低剂量自身抗原不会被交叉呈递，因此被忽略。因此，免疫系统在外周采用两种策略来避免CD8 + T细胞介导的自身免疫：清除对高剂量自身抗原产生反应的自身反应性CD8 + T细胞，以及忽略低浓度表达的自身抗原。
