title: Antigen-specific transfer of functional programmed death ligand 1 from human APCs onto CD8+ T cells via trogocytosis.
abstract: Upon specific interaction with APCs, T cells capture membrane fragments and surface molecules in a process termed trogocytosis. In this study, we demonstrate that human Ag-specific CD8(+) T cells acquire the coinhibitory molecule programmed death ligand 1 (PD-L1) from mature dendritic cells (mDC) and tumor cells in an Ag-specific manner. Immature dendritic cells were less effective in transferring surface molecules onto CD8(+) T cells than mDCs. Interestingly, trogocytosis of PD-L1 requires cell-cell contact and cannot be induced by uptake of soluble proteins obtained from mDC lysates. The transfer process is impaired by inhibition of vacuolar ATPases in T cells as well as by fixation of dendritic cells. Of importance, CD8(+) T cells that acquired PD-L1 complexes were able to induce apoptosis of neighboring programmed death 1-expressing CD8(+) T cells. In summary, our data demonstrate that human CD8(+) T cells take up functionally active PD-L1 from APCs in an Ag-specific fashion, leading to fratricide of programmed death 1-expressing, neighboring T cells. The transfer of functionally active coinhibitory molecules from APCs onto human CD8(+) T cells could have a regulatory role in immune responses.
authors.affiliation: Department of Internal Medicine 5, Hematology and Oncology, University of Erlangen-Nuremberg, Erlangen, D-91054, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Gary
authors.forename: Simon
authors.initials: S
authors.lastname: Voelkl
authors.forename: Ralf
authors.initials: R
authors.lastname: Palmisano
authors.forename: Evelyn
authors.initials: E
authors.lastname: Ullrich
authors.forename: Jacobus J
authors.initials: JJ
authors.lastname: Bosch
authors.forename: Andreas
authors.initials: A
authors.lastname: Mackensen
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism*; D060890:B7-H1 Antigen / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002450:Cell Communication / Q000276:immunology*; D016923:Cell Death / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008546:Melanoma, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D021381:Protein Transport / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D018984:Epitopes, T-Lymphocyte