Lewis X oligosaccharides targeting to DC-SIGN enhanced antigen-specific immune response.
Dendritic cell-specific intercellular-adhesion-molecule-grabbing non-integrin (DC-SIGN) is a potential target receptor for vaccination purposes. In the present study, we employed Lewis X (Le(x)) oligosaccharides, which mimic natural ligands, to target ovalbumin (OVA) to human dendritic cells (DCs) via DC-SIGN, to investigate the effect of this DC-SIGN-targeting strategy on the OVA-specific immune response. We demonstrated that Le(x) oligosaccharides could enhance the OVA-specific immune response as determined by enzyme-linked immunospot assay (ELISPOT), intracellular interferon-gamma staining and (51)Cr-release assay. An almost 300-fold lower dose of Le(x)-OVA induced balanced interferon-gamma-secreting cells compared to OVA alone. Furthermore, secretion of interleukin-10, a reported mediator of immune suppression related to DC-SIGN, was not increased by Le(x)-OVA, either alone or together with sCD40L-stimulated groups. A blocking antibody against DC-SIGN (12507) reduced the numbers of interferon-gamma-secreting cells during Le(x)-OVA stimulation, yet it did not prevent Le(x) oligosaccharides from promoting the secretion of interleukin-10 that was induced by ultra-pure lipopolysaccharide. These results suggested that the strategy of DC-SIGN targeting mediated by Le(x) oligosaccharides could promote a T-cell response. This DC-targeting may imply a novel vaccination strategy.
Wang
Jingxue
J
Institute of Immunology PLA, The Third Military Medical University, Chongqing, China.
Zhang
Yongmin
Y
Wei
Jing
J
Zhang
Xiaoping
X
Zhang
Bei
B
Zhu
Zhenyuan
Z
Zou
Wei
W
Wang
Yiqin
Y
Mou
Zhirong
Z
Ni
Bin
B
Wu
Yuzhang
Y
D000941:Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000276:immunology*; D007983:Lewis Blood Group Antigens; D008213:Lymphocyte Activation / Q000276:immunology; D009844:Oligosaccharides / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000941:Antigens; D015815:Cell Adhesion Molecules; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma; D016753:Interleukin-10; D037181:Lectins, C-Type; D007983:Lewis Blood Group Antigens; D009844:Oligosaccharides; D010047:Ovalbumin; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C494219:Lewis a oligosaccharide