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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Wang, Weigang Carper, Katie Malone, Frances Latchman, Yvette Perkins, James Fu, Yaowen Reyes, Jorge Li, Wei |
| Description | Country affiliation: United States Author Affiliation: Wang W ( Division of Transplantation, Department of Surgery, University of Washington Medical Center, Seattle, WA 98195, USA.) |
| Abstract | BACKGROUND: PD-L1, a ligand for programmed death 1 (PD-1), delivers a negative costimulatory signal to T cells and plays a critical role in the regulation of peripheral tolerance. METHODS: We used PD-L1(-/-) mice to evaluate the role of the PD-L1 signal on allogeneic immune responses in vivo and the underlying mechanisms. Heart transplantation was performed from PD-L1(-/-) donors or recipients in major histocompatibility complex fully mismatched mouse combinations. The immunologic function of allograft recipients was evaluated ex vivo by enzyme-linked immunospot, mixed lymphocytes reaction, cytotoxic T lymphocyte, and flow cytometry. RESULTS: Our results demonstrated that PD-L1(-/-) T cells proliferated vigorously under alloantigen stimulation, and also that the antigen-presenting cells (APCs) from PD-L1(-/-) mice exhibited a stronger allostimulatory activity compared with that in wild-type mice. Heart allografts were rejected at an accelerated rate in both PD-L1(-/-) donors and recipients. This was associated with significantly augmented donor specific T-cell proliferation and antidonor cytotoxic T lymphocyte activities, and enhanced Th1- or Th2-type immune responses of heart allograft recipients. CONCLUSIONS: Absence of PD-L1 input triggers a stimulatory signal to effector T cells and APCs, accelerating heart allograft rejection. Engagement of the PD-L1 signal on T cells or APCs may be necessary to induce transplant tolerance. |
| File Format | HTM / HTML |
| ISSN | 00411337 |
| Issue Number | 6 |
| Volume Number | 86 |
| e-ISSN | 15346080 |
| Journal | Transplantation Journal |
| Language | English |
| Publisher | Lippincott Williams & Wilkins |
| Publisher Date | 2008-09-27 |
| Publisher Place | United States |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Transplantation Antigens, Cd80 Immunology Antigens, Differentiation Genetics Graft Rejection Heart Transplantation Membrane Glycoproteins Deficiency Peptides Transplantation, Homologous Animals Antigens, Cd274 Cd4-positive T-lymphocytes Cd8-positive T-lymphocytes Enzyme-linked Immunosorbent Assay Killer Cells, Natural Lymphocyte Activation Lymphocyte Culture Test, Mixed Major Histocompatibility Complex Mice Mice, Inbred Balb C Mice, Inbred C3h Mice, Inbred C57bl Mice, Knockout Programmed Cell Death 1 Receptor Spleen T-lymphocytes Time Factors Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Transplantation |
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