In vivo targeting of DC-SIGN-positive antigen-presenting cells in a nonhuman primate model.
In vivo targeting of antigen-presenting cells (APCs) with antigens coupled to antibodies directed against APC-specific endocytic receptors is a simple and a promising approach to induce or modulate immune responses against those antigens. In a recent in vitro study, we have shown that targeting of APCs with an antigen coupled to an antibody directed against the endocytic receptor DC-SIGN effectively induces a specific immune response against that antigen. The aim of the present study was to determine the ability of the murine antihuman DC-SIGN antibody AZN-D1 to target APCs in a cynomolgus macaque model after its administration in vivo. Immunohistochemical analysis demonstrated that macaques injected intravenously with AZN-D1 have AZN-D1-targeted APCs in all lymph nodes (LNs) tested and in the liver. DC-SIGN-positive cells were mainly located in the medullary sinuses of the LNs and in the hepatic sinusoids in the liver. No unlabeled DC-SIGN molecules were found in the LN of AZN-D1-injected macaques. Morphologic criteria and staining of sequential LN sections with a panel of antibodies indicated that the DC-SIGN-targeted cells belong to the myeloid lineage of APCs. In conclusion, this is the first study that shows specific targeting of APCs in vivo by using antibodies directed against DC-SIGN.
Pereira
Cândida F
CF
Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Torensma
Ruurd
R
Hebeda
Konnie
K
Kretz-Rommel
Anke
A
Faas
Susan J
SJ
Figdor
Carl G
CG
Adema
Gosse J
GJ
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D007728:Kupffer Cells / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008221:Lymphoid Tissue / Q000276:immunology*; D008252:Macaca fascicularis; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin