Article: article from journal or magazin.
Cross-presenting human gammadelta T cells induce robust CD8+ alphabeta T cell responses.
Proceedings of the National Academy of Sciences of the United States of America
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
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.
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
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