Direct Exosome Stimulation of Peripheral Human T Cells Detected by Elispot.
From: Karolinska University Hospital and Institutet, Department of Medicine, Clinical Allergy Research Unit, Stockholm, Sweden. Charlotte.Admyre@cfa.ki.se
European journal of immunology
- Publish Date: Jul 2006
- ISSN: 0014-2980
- Volume: 36
- Issue: 7
- Pages: 1772-81
- Medium: Print
- Language: English
- Citation (JAMA): Admyre Charlotte, Johansson Sara M, Paulie Staffan, et al. Direct Exosome Stimulation of Peripheral Human T Cells Detected by Elispot.. Eur. J. Immunol. Jul 2006;36:1772-81
Abstract
Exosomes from APC are nano-vesicles that can induce antigen-specific T cell responses and are presently explored as therapeutic tools in different clinical settings. Investigations of the capacity of exosomes to stimulate T cells in vitro have mostly been performed on T cell hybridomas, clones or lines. Whether exosomes can stimulate T cells directly or need the presence of dendritic cells (DC) is debated. We could detect exosome-induced antigen-specific CD8(+) T cell responses in peripheral blood from humans. Exosomes from monocyte-derived DC (MDDC) were loaded with a mix of 23 immunogenic peptides from EBV, CMV and influenza virus, and added to autologous peripheral CD8(+) T cells. IFN-gamma-producing cells were detected by enzyme-linked immunospot assay (ELISPOT). MDDC-exosomes induced IFN-gamma production in CD8(+) T cells without addition of DC. The response was exosome dose dependent, and dependent on exosomal MHC class I. Furthermore, we detected an enhanced T cell stimulatory capacity by exosomes from lipopolysaccharide-matured MDDC compared to exosomes from immature MDDC. Exosomes could also induce TNF-alpha production. These results show, for the first time, that exosomes can directly stimulate human peripheral CD8(+) T cells in an antigen-specific manner and that ELISPOT is a suitable method for detecting exosome-induced peripheral T cell responses. This system may provide a useful tool when developing exosomes as therapeutic agents.
Mesh Headings (Keywords): Cells, Cultured, Cytoplasmic Vesicles, Dendritic Cells, Enzyme-Linked Immunosorbent Assay, Humans, Lymphocyte Activation, Microscopy, Immunoelectron, T-Lymphocytes
Check for Full Text / PubMed Unique Identifier (PMID): 16761310
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