Preferential induction of CD4+ T cell responses through in vivo targeting of antigen to dendritic cell-associated C-type lectin-1
Preferential induction of CD4+ T cell responses through in vivo targeting of antigen to dendritic cell-associated C-type lectin-1
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DOI：
10.4049/jimmunol.177.4.2276
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发表时间：
2006-08-15
影响因子：
4.4
通讯作者：
Tough, David F.
中科院分区：
文献类型：
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作者：
Carter, Robert W.;Thompson, Clare;Tough, David F.
以树突状细胞 (DC) 为靶点的抗原和治疗药物在免疫治疗和疫苗接种方面具有巨大潜力。由于 DC 是异质的，最佳靶向策略需要了解 DC 亚群之间的功能专业化以及识别用于靶向适当 DC 的分子。我们表征了小鼠 DC 亚群上真菌识别受体 DC 相关 C 型凝集素 1 (Dectin-1) 的表达，并研究了抗 Dectin-1 Ab 递送 Ag 刺激免疫反应的能力。 Dectin-1 在脾脏和淋巴结中发现的 CD8 α(-)CD4(-)CD11b(+) DC 以及皮肤和皮下的真皮 DC 上表达。淋巴结。注射Ag-抗Dectin-1缀合物在低剂量下诱导CD4(+)和CD8(+) T细胞和Ab反应，而游离Ag未能引起反应。值得注意的是，将 Ag 靶向 Dectin-1 与 CD205（一种在 CD8 α(+)CD4(-)CD11b(-) DC、真皮 DC 和朗格汉斯细胞上表达的分子）产生了性质不同的免疫反应。与抗 Dectin-1 不同，抗 CD205 缀合物未能引发 Ab 反应。此外，当静脉注射缀合物时，与抗CD205相比，抗Dectin-1刺激的CD4(+) T细胞反应强得多，而CD8(+) T细胞反应弱得多。结果表明 Dectin-1 是一种潜在的免疫靶向分子，并对 DC 亚群的特化具有影响。
Targeting of Ags and therapeutics to dendritic cells (DCs) has immense potential for immunotherapy and vaccination. Because DCs are heterogeneous, optimal targeting strategies will require knowledge about functional specialization among, DC subpopulations and identification of molecules for targeting appropriate DCs. We characterized the expression of a fungal recognition receptor, DC-associated C-type lectin-1 (Dectin-1), on mouse DC subpopulations and investigated the ability of an anti-Dectin-1 Ab to deliver Ag for the stimulation of immune responses. Dectin-1 was shown to be expressed on CD8 alpha(-)CD4(-)CD11b(+) DCs found in spleen and lymph nodes and dermal DCs present in skin and s.c. lymph nodes. Injection of Ag-anti-Dectin-1 conjugates induced CD4(+) and CD8(+) T cell and Ab responses at low doses where free Ag failed to elicit a response. Notably, qualitatively different immune responses were generated by targeting Ag to Dectin-1 vs CD205, a molecule expressed on CD8 alpha(+)CD4(-)CD11b(-) DCs, dermal DCs, and Langerhans cells. Unlike anti-Dectin-1, anti-CD205 conjugates failed to elicit an Ab response. Moreover, when conjugates were injected i.v., anti-Dectin-1 stimulated a much stronger CD4(+) T cell response and a much weaker CD8(+) T cell response than anti-CD205. The results reveal Dectin-1 as a potential targeting molecule for immunization and have implications for the specialization of DC subpopulations.