Cross-presenting human gammadelta T cells induce robust CD8+ alphabeta T cell responses.

Details

Serval ID
serval:BIB_9E0CB6E72231
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cross-presenting human gammadelta T cells induce robust CD8+ alphabeta T cell responses.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Brandes M., Willimann K., Bioley G., Lévy N., Eberl M., Luo M., Tampé R., Lévy F., Romero P., Moser B.
ISSN
1091-6490[electronic]
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
106
Number
7
Pages
2307-2312
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
Gammadelta T cells are implicated in host defense against microbes and tumors but their mode of function remains largely unresolved. Here, we have investigated the ability of activated human Vgamma9Vdelta2(+) T cells (termed gammadelta T-APCs) to cross-present microbial and tumor antigens to CD8(+) alphabeta T cells. Although this process is thought to be mediated best by DCs, adoptive transfer of ex vivo antigen-loaded, human DCs during immunotherapy of cancer patients has shown limited success. We report that gammadelta T-APCs take up and process soluble proteins and induce proliferation, target cell killing and cytokine production responses in antigen-experienced and naïve CD8(+) alphabeta T cells. Induction of APC functions in Vgamma9Vdelta2(+) T cells was accompanied by the up-regulation of costimulatory and MHC class I molecules. In contrast, the functional predominance of the immunoproteasome was a characteristic of gammadelta T cells irrespective of their state of activation. Gammadelta T-APCs were more efficient in antigen cross-presentation than monocyte-derived DCs, which is in contrast to the strong induction of CD4(+) alphabeta T cell responses by both types of APCs. Our study reveals unexpected properties of human gammadelta T-APCs in the induction of CD8(+) alphabeta T effector cells, and justifies their further exploration in immunotherapy research.
Keywords
Allergy and Immunology, Antigen Presentation, CD4-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/immunology, Dendritic Cells/cytology, Dendritic Cells/immunology, HLA-A2 Antigen/chemistry, Histocompatibility Antigens Class I/genetics, Humans, Immunotherapy/methods, Models, Biological, Mycobacterium tuberculosis, Neoplasms/immunology, Proteasome Endopeptidase Complex/metabolism, Receptors, Antigen, T-Cell, alpha-beta/metabolism, Receptors, Antigen, T-Cell, gamma-delta/metabolism, T-Lymphocytes/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
15/01/2010 15:21
Last modification date
20/08/2019 15:04
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