Natural killer T (NKT)-B-cell interactions promote prolonged antibody responses and long-term memory to pneumococcal capsular polysaccharides
Natural killer T (NKT)-B-cell interactions promote prolonged antibody responses and long-term memory to pneumococcal capsular polysaccharides
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DOI：
10.1073/pnas.1303218110
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发表时间：
2013-10-01
影响因子：
11.1
通讯作者：
Bendelac, Albert
中科院分区：
文献类型：
--
作者：
Bai, Li;Deng, Shenglou;Bendelac, Albert
先天样自然杀伤T （NKT）细胞通过识别表达cd1的抗原呈递细胞呈递的保守微生物脂质抗原，并提供CD40L和细胞因子信号，从而增强细胞和体液对感染的免疫。尽管NKT细胞有效地将树突状细胞授权给主要的有效效应T细胞和记忆T细胞，但基于模型抗原（如α半乳糖神经酰胺-硝基苯偶联物）的研究得出结论，对B细胞的帮助与NKT滤泡辅助分化有关，但仅限于短期反应，没有诱导记忆。我们在细胞外包膜病原体肺炎链球菌的背景下重新审视了这一令人惊讶的结论，其中NKT细胞和B细胞分别对脂质和包膜多糖抗原的识别提供了关键的宿主保护。使用脂质体纳米颗粒显示合成脂质和多糖抗原，在体内诱导纯粹和直接的NKT- b细胞相互作用，我们观察到强烈和持久的抗体反应，具有同型开关，亲和成熟和持久的b细胞记忆，尽管适度或不存在NKT滤泡辅助分化。此外，Cd1d的条件消融表明需要两步过程，首先是与树突状细胞的同源相互作用，以激活NKT细胞，然后是与B细胞的同源相互作用，以诱导同型转换和记忆。因此，NKT对B细胞的帮助既是抗菌防御的一个主要方面，也是B细胞疫苗的一个有希望的靶点。
Innate-like natural killer T (NKT) cells critically enhance cell and humoral immunity against infections through recognition of conserved microbial lipid antigens presented by CD1d-expressing antigen-presenting cells, and provision of CD40L and cytokine signals. Whereas NKT cells efficiently licensed dendritic cells to prime potent effector and memory T cells, studies based on model antigens such as alphagalactosylceramide-nitrophenyl conjugates concluded that help to B cells was associated with NKT follicular helper differentiation, but limited to short-term responses without induction of memory. We revisited this surprising conclusion in the context of the extracellular encapsulated pathogen Streptococcus pneumoniae, where recognition of lipid and capsular polysaccharide antigens by NKT cells and B cells, respectively, provide critical host protection. Using liposomal nanoparticles displaying synthetic lipid and polysaccharide antigens to elicit pure and direct NKT-B-cell interactions in vivo, we observed intense and prolonged antibody responses with isotype switch, affinity maturation, and long-lasting B-cell memory, despite modest or absent NKT follicular helper differentiation. Furthermore, conditional ablation of Cd1d demonstrated a requirement for a two-step process involving first cognate interactions with dendritic cells, for NKT cell activation, and then with B cells, for induction of isotype switch and memory. Thus, NKT help to B cells represents both a major arm of antimicrobial defense and a promising target for B-cell vaccines.