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Eur J Immunol. 2012 Jul;42(7):1778-84. doi: 10.1002/eji.201141978.

Plasma-derived MHC class II+ exosomes from tumor-bearing mice suppress tumor antigen-specific immune responses.

Author information

1
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.

Abstract

Tumor-specific immunosuppression is frequently observed in tumor-bearing hosts. Exosomes are nano-sized, endosomal-derived membrane vesicles secreted by most tumor and hematopoietic cells and have been shown to actively participate in immune regulation. We previously demonstrated that antigen-specific immunosuppressive exosomes could be isolated from the blood plasma of antigen-immunized mice. Here, we demonstrate that plasma-derived exosomes isolated from mice bearing OVA-expressing tumors were able to suppress OVA-specific immune responses in a mouse delayed-type hypersensitivity model. Enrichment of tumor-derived exosomes in the plasma of mice bearing subcutaneous melanoma was not detected using an exosome-tagging approach. Instead, depletion of MHC class II(+) vesicles from plasma-derived exosomes or using plasma-derived exosomes isolated from MHC class II-deficient mice resulted in significant abrogation of the suppressive effect. These results demonstrate that circulating host-derived, MHC class II(+) exosomes in tumor-bearing hosts are able to suppress the immune response specific to tumor antigens.

PMID:
22585706
PMCID:
PMC3471134
DOI:
10.1002/eji.201141978
[Indexed for MEDLINE]
Free PMC Article

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