Conventional type 1 dendritic cells induce TH1, TH1‐like follicular helper T cells and regulatory T cells after antigen boost via DEC205 receptor

• Published in: European journal of immunology Vol. 50; no. 12; pp. 1895 - 1911
• Main Authors: Sulczewski, Fernando Bandeira, Martino, Larissa Alves, Almeida, Bianca da Silva, Zaneti, Arthur Baruel, Ferreira, Natália Soares, Amorim, Kelly Nazaré da Silva, Yamamoto, Márcio Massao, Apostolico, Juliana de Souza, Rosa, Daniela Santoro, Boscardin, Silvia Beatriz
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 01.12.2020
• Subjects: Antibody response; Antigen presentation; antigen targeting; Antigens; Cell differentiation; Class switching; DCIR2; DEC205; Dendritic cells; Immunization; Immunoglobulin G; Immunoregulation; Inflammation; Lymphocytes; Lymphocytes T; Monoclonal antibodies; Poly (I:C); Spleen
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.202048694

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. cDC1s and cDC2s differentially promote CD4+ T cell responses. Antigen targeting to cDC1s induces TH1 cells after prime, and TReg and TH1‐like TFH cells after boost. In contrast, antigen delivery to cDC2s elicits TFH cells, GC, and plasma cells after prime, and TH2/TH17 after boost.