T cell ignorance is bliss: T cells are not tolerized by Langerhans cells presenting human papillomavirus antigens in the absence of costimulation.
T cell ignorance is bliss: T cells are not tolerized by Langerhans cells presenting human papillomavirus antigens in the absence of costimulation.
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DOI：
10.1016/j.pvr.2016.01.002
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发表时间：
2016-12
期刊：
影响因子：
--
通讯作者：
Kast WM
中科院分区：
文献类型：
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作者：
Woodham AW;Yan L;Skeate JG;van der Veen D;Brand HH;Wong MK;Da Silva DM;Kast WM
人乳头瘤病毒16型（HPV 16）感染是上皮内的，因此，已知HPV 16与朗格汉斯细胞（LC）（常驻上皮抗原呈递细胞（APC））相互作用。目前APC介导的T细胞无反应性诱导的范例是通过MHC分子上的肽传递T细胞受体信号（信号1），但没有共刺激（信号2）。我们以前证明，在体外暴露于HPV 16的LC在没有共刺激的情况下将HPV抗原呈递给T细胞，但是仍然不确定这样的T细胞是否会保持无知，变得无反应性，或者在CD4+ T细胞的情况下，分化为TcB。在这里，我们证明了TcB不是由仅呈递信号1的LC诱导的，并且通过一系列体外免疫表明，在持续接收信号1后数周从LC接收信号1+2的CD8+ T细胞能够具有稳健的效应子功能。重要的是，这表明T细胞没有耐受，而是对HPV保持无知，并在适当的信号下被激活。
Human papillomavirus type 16 (HPV16) infections are intra-epithelial, and thus, HPV16 is known to interact with Langerhans cells (LCs), the resident epithelial antigen-presenting cells (APCs). The current paradigm for APC-mediated induction of T cell anergy is through delivery of T cell receptor signals via peptides on MHC molecules (signal 1), but without costimulation (signal 2). We previously demonstrated that LCs exposed to HPV16 in vitro present HPV antigens to T cells without costimulation, but it remained uncertain if such T cells would remain ignorant, become anergic, or in the case of CD4+ T cells, differentiate into Tregs. Here we demonstrate that Tregs were not induced by LCs presenting only signal 1, and through a series of in vitro immunizations show that CD8+ T cells receiving signal 1+2 from LCs weeks after consistently receiving signal 1 are capable of robust effector functions. Importantly, this indicates that T cells are not tolerized but instead remain ignorant to HPV, and are activated given the proper signals.