Cross-presenting human gammadelta T cells induce robust CD8+ alphabeta T cell responses.
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.
Brandes
Marlène
M
Institute of Cell Biology, University of Bern, CH-3000 Bern 9, Switzerland.
Willimann
Katharina
K
Bioley
Gilles
G
Lévy
Nicole
N
Eberl
Matthias
M
Luo
Ming
M
Tampé
Robert
R
Lévy
Frédéric
F
Romero
Pedro
P
Moser
Bernhard
B
D000486:Allergy and Immunology; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000737:chemistry; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008954:Models, Biological; D009169:Mycobacterium tuberculosis; D009369:Neoplasms / Q000276:immunology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D046988:Proteasome Endopeptidase Complex