The CD169 sialoadhesin molecule mediates cytotoxic T‐cell responses to tumour apoptotic vesicles

Apoptosis leads to the fragmentation and packaging of cellular contents into discrete vesicles, a process known as ‘blebbing’. Extracellular vesicles express membrane‐bound sialic acids, which enable their capture by CD169 (sialoadhesin; Siglec‐1) expressing macrophages in the lymph node and spleen....

Full description

Saved in:
Bibliographic Details
Published in:Immunology and cell biology 2016-05, Vol.94 (5), p.430-438
Main Authors: Black, Lane VC, Saunderson, Sarah C, Coutinho, Frazer P, Muhsin‐Sharafaldine, Morad‐Rémy, Damani, Tanvi T, Dunn, Amy C, McLellan, Alexander D
Format: Article
Language:English
Subjects:
Animals
Apoptosis - drug effects
Biotinylation
Cell Line, Tumor
Cytotoxicity, Immunologic - drug effects
Doxorubicin - pharmacology
Extracellular Vesicles - drug effects
Extracellular Vesicles - metabolism
Extracellular Vesicles - ultrastructure
Lymphoma - immunology
Lymphoma - pathology
Mice, Inbred C57BL
Sialic Acid Binding Ig-like Lectin 1 - metabolism
Staurosporine - pharmacology
T-Lymphocytes, Cytotoxic - drug effects
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Apoptosis leads to the fragmentation and packaging of cellular contents into discrete vesicles, a process known as ‘blebbing’. Extracellular vesicles express membrane‐bound sialic acids, which enable their capture by CD169 (sialoadhesin; Siglec‐1) expressing macrophages in the lymph node and spleen. Furthermore, CD169 mediates vesicle trafficking and suppresses the immune response to exosomes—a type of extracellular vesicle released from living cells. In this study, we found that CD169+ macrophages were the predominant splenic macrophage subset responsible for the capture of EL4 lymphoma‐derived apoptotic vesicles (ApoVs) from circulation. CD169−/− mice had significantly enhanced in vivo cytotoxic T lymphocyte responses to antigen‐pulsed ApoVs, indicating a suppressive role for CD169+ macrophages to ApoV‐associated antigen. In contrast to the observed immunogenic role of ApoVs, the co‐administration of unpulsed ApoVs with antigen‐pulsed dendritic cells (DCs) significantly suppressed DC‐mediated cytotoxic response in vivo; however, this occurred independent of CD169 expression. Overall, our results confirm that apoptosis contributes to both tolerance and immunity, as well as establishing CD169 as a critical mediator of the immune response to extracellular vesicles.
ISSN:0818-9641
1440-1711
DOI:10.1038/icb.2015.111