Transcutaneous immunization induces mucosal CTLs and protective immunity by migration of primed skin dendritic cells.
Transcutaneous immunization induces mucosal CTLs and protective immunity by migration of primed skin dendritic cells.
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经皮免疫通过引发的皮肤树突状细胞的迁移诱导粘膜 CTL 和保护性免疫。
DOI：
10.1172/jci20261
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Berzofsky,JayA
中科院分区：
文献类型：
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作者：
Belyakov,IgorM;Hammond,ScottA;Ahlers,JeffreyD;Glenn,GregoryM;Berzofsky,JayA
经皮免疫（TCI），即在皮肤上应用疫苗，可在动物模型和人类中诱导强大的全身和粘膜抗体。 TCI 引发针对疫苗抗原的粘膜免疫反应的方式尚未得到很好的表征。我们研究了 TCI 与 HIV 肽疫苗对诱导小鼠粘膜和全身 CTL 反应以及针对活病毒粘膜攻击的保护性免疫的影响。 TCI 后，在脾脏和肠粘膜中检测到了强烈的 HIV 特异性 CTL 反应。这些反应取决于佐剂的添加，并导致针对编码 HIV gp160 的重组痘苗病毒的粘膜攻击的保护。虽然很明显，佐剂激活的 DC 主要迁移至引流淋巴结，但与特定 T 细胞共培养以及 TCI 后从派尔氏淋巴结分离的 DC 进行流式细胞术研究表明，携带皮肤源性抗原的激活 DC 也从皮肤迁移至肠粘膜中的免疫诱导位点，并将抗原直接呈递给驻留淋巴细胞。这些结果和之前的临床试验结果支持这样的观察：TCI 是诱导强粘膜抗体和 CTL 反应的安全有效的策略。
Transcutaneous immunization (TCI), the application of vaccines on the skin, induces robust systemic and mucosal antibodies in animal models and in humans. The means by which mucosal immune responses to vaccine antigens are elicited by TCI has not been well characterized. We examined the effect of TCI with an HIV peptide vaccine on the induction of mucosal and systemic CTL responses and protective immunity against mucosal challenge with live virus in mice. Robust HIV-specific CTL responses in the spleen and in the gut mucosa were detected after TCI. The responses were dependent upon the addition of an adjuvant and resulted in protection against mucosal challenge with recombinant vaccinia virus encoding HIV gp160. Although it is clear that adjuvant-activated DCs migrated mainly to draining lymph nodes, coculture with specific T cells and flow cytometry studies with DCs isolated from Peyer’s patches after TCI suggested that activated DCs carrying skin-derived antigen also migrated from the skin to immune-inductive sites in gut mucosa and presented antigen directly to resident lymphocytes. These results and previous clinical trial results support the observation that TCI is a safe and effective strategy for inducing strong mucosal antibody and CTL responses.