Antigen-specific transfer of functional programmed death ligand 1 from human APCs onto CD8+ T cells via trogocytosis

• Published in: The Journal of immunology (1950) 2012-01, Vol.188 (2), p.744-752
• Main Authors: Gary, Regina, Voelkl, Simon, Palmisano, Ralf, Ullrich, Evelyn, Bosch, Jacobus J, Mackensen, Andreas
• Format: Article
• Language: English
• Subjects: Antigen Presentation - immunology; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; B7-H1 Antigen - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Communication - immunology; Cell Death - immunology; Cell Line, Tumor; Cells, Cultured; Epitopes, T-Lymphocyte - immunology; Epitopes, T-Lymphocyte - metabolism; Humans; Melanoma, Experimental - immunology; Melanoma, Experimental - metabolism; Melanoma, Experimental - pathology; Protein Transport - immunology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1101412

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.