The Programmed Death (PD)‐1/PD‐Ligand 1 Pathway Regulates Graft‐Versus‐Host‐Reactive CD8 T Cells After Liver Transplantation
| Autor: | Wolfgang Herr, M. Schuchmann, Gerd Otto, Abdo Konur, E von Stebut, O. Schreiner, S. Gregor, P R Galle, Eva Distler, Elke Schnürer, T Wölfel, J Kuball, Christoph Huber, Matthias Theobald, Ralf G. Meyer |
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| Rok vydání: | 2008 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male Cell Transplantation Programmed Cell Death 1 Receptor Graft vs Host Disease CD8-Positive T-Lymphocytes TCIRG1 Mice Interleukin 21 Immune system Antigen Antigens CD Animals Humans Immunology and Allergy Cytotoxic T cell Medicine Pharmacology (medical) IL-2 receptor Mice Knockout Transplantation business.industry Interleukin-2 Receptor alpha Subunit Forkhead Transcription Factors Middle Aged Liver Transplantation surgical procedures operative Gene Expression Regulation Antigens Surface Immunology Interleukin 12 Apoptosis Regulatory Proteins business Immunosuppressive Agents |
| Zdroj: | American Journal of Transplantation. 8:2434-2444 |
| ISSN: | 1600-6135 |
| DOI: | 10.1111/j.1600-6143.2008.02401.x |
| Popis: | Acute graft-versus-host disease (aGVHD) is a life-threatening complication after solid-organ transplantation, which is mediated by host-reactive donor T cells emigrating from the allograft. We report on two liver transplant recipients who developed an almost complete donor chimerism in peripheral blood and bone marrow-infiltrating T cells during aGVHD. By analyzing these T cells directly ex vivo, we found that they died by apoptosis over time without evidence of rejection by host T cells. The host-versus-donor reactivity was selectively impaired, as anti-third-party and antiviral T cells were still detectable in the host repertoire. These findings support the acquired donor-specific allotolerance concept previously established in animal transplantation studies. We also observed that the resolution of aGVHD was not accompanied by an expansion of circulating immunosuppressive CD4/CD25/FoxP3-positive T cells. In fact, graft-versus-host-reactive T cells were controlled by an alternative negative regulatory pathway, executed by the programmed death (PD)-1 receptor and its ligand PD-L1. We found high PD-1 expression on donor CD4 and CD8 T cells. In addition, blocking PD-L1 on host-derived cells significantly enhanced alloreactivity by CD8 T cells in vitro. We suggest the interference with the PD-1/PD-L1 pathway as a therapeutic strategy to control graft-versus-host-reactive T cells in allograft recipients. |
| Databáze: | OpenAIRE |
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