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Conventional type 1 dendritic cells induce TH 1, TH 1-like follicular helper T cells and regulatory T cells after antigen boost via DEC205 receptor.
European Journal of Immunology ( IF 5.4 ) Pub Date : 2020-07-16 , DOI: 10.1002/eji.202048694
Fernando Bandeira Sulczewski 1 , Larissa Alves Martino 1 , Bianca da Silva Almeida 1 , Arthur Baruel Zaneti 1 , Natália Soares Ferreira 1 , Kelly Nazaré da Silva Amorim 1 , Márcio Massao Yamamoto 1 , Juliana de Souza Apostolico 2 , Daniela Santoro Rosa 2, 3 , Silvia Beatriz Boscardin 1, 3
Affiliation  

Conventional dendritic cells (cDCs) are specialized in antigen presentation. In the mouse spleen, cDCs are classified in cDC1s and cDC2s, and express DEC205 and DCIR2 endocytic receptors, respectively. Monoclonal antibodies (mAbs) αDEC205 (αDEC) and αDCIR2 have been fused to different antigens to deliver them to cDC1s or cDC2s. We immunized mice with αDEC and αDCIR2 fused to an antigen using Poly(I:C) as adjuvant. The initial immune response was analyzed from days 3 to 6 after the immunization. We also studied the influence of a booster dose. Our results showed that antigen targeting to cDC1s promoted a pro‐inflammatory TH1 cell response. Antigen targeting to cDC2s induced TFH cells, GCs, and plasma cell differentiation. After boost, antigen targeting to cDC1s improved the TH1 cell response and induced TH1‐like TFH cells that led to an increase in specific antibody titers and IgG class switch. Additionally, a population of regulatory T cells was also observed. Antigen targeting to cDC2s did not improve the specific antibody response after boost. Our results add new information on the immune response induced after the administration of a booster dose with αDEC and αDCIR2 fusion mAbs. These results may be useful for vaccine design using recombinant mAbs.

中文翻译:

常规的1型树突状细胞在通过DEC205受体增强抗原后诱导TH 1,TH 1样卵泡辅助性T细胞和调节性T细胞。

常规树突状细胞(cDC)专门用于抗原呈递。在小鼠脾脏中,cDCs分为cDC1s和cDC2s,分别表达DEC205和DCIR2内吞受体。单克隆抗体(mAb)αDEC205(αDEC)和αDCIR2已与不同的抗原融合,以将其递送至cDC1s或cDC2s。我们使用融合了抗原的αDEC和αDCIR2免疫小鼠,使用Poly(I:C)作为佐剂。免疫后第3至6天分析初始免疫应答。我们还研究了加强剂量的影响。我们的结果表明,靶向cDC1s的抗原可促进促炎性T H 1细胞反应。靶向cDC2的抗原可诱导T FH细胞,GC和浆细胞分化。加强免疫后,靶向cDC1s的抗原改善了TH 1细胞反应和诱导的T H 1样T FH细胞,导致特异性抗体滴度和IgG类转换增加。另外,还观察到了调节性T细胞的群体。加强免疫后,靶向cDC2的抗原不能改善特异性抗体反应。我们的研究结果增加了与αDEC和αDCIR2融合单克隆抗体一起加强剂量给药后诱导的免疫应答的新信息。这些结果对于使用重组mAb的疫苗设计可能是有用的。
更新日期:2020-07-16
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