Deletion of cognate CD8 T cells by immature dendritic cells: a novel role for perforin, granzyme A, TREM-1, and TLR7
| Autor: | Oren Milstein, Yumi Ito, Yaki Eidelstein, Elias Shezen, Esther Bachar-Lustig, Vera Shinder, Yair Reisner, Yael Zlotnikov Klionsky, David Hagin, Steffen Jung, Toshiyuki Takai, Lior Zangi, Assaf Lask, Liran Yarimi, Shlomit Reich-Zeliger |
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| Rok vydání: | 2012 |
| Předmět: |
Immunology
Population Cell Culture Techniques CD8-Positive T-Lymphocytes Biochemistry Granzymes Major Histocompatibility Complex Mice Cytotoxic T cell Animals Receptors Immunologic education Cells Cultured education.field_of_study Membrane Glycoproteins biology Perforin Cell Biology Hematology Dendritic Cells Hematopoietic Stem Cells Triggering Receptor Expressed on Myeloid Cells-1 Cell biology Transplantation Mice Inbred C57BL Haematopoiesis src-Family Kinases Granzyme Toll-Like Receptor 7 Granzyme A biology.protein Female CD8 |
| Zdroj: | Blood. 120(8) |
| ISSN: | 1528-0020 |
| Popis: | Immature dendritic cells (imDCs) can have a tolerizing effect under normal conditions or after transplantation. However, because of the significant heterogeneity of this cell population, it is extremely difficult to study the mechanisms that mediate the tolerance induced or to harness the application of imDCs for clinical use. In the present study, we describe the generation of a highly defined population of imDCs from hematopoietic progenitors and the direct visualization of the fate of TCR-transgenic alloreactive CD4+ and CD8+ T cells after encountering cognate or noncognate imDCs. Whereas CD4+ T cells were deleted via an MHC-independent mechanism through the NO system, CD8+ T-cell deletion was found to occur through a unique MHC-dependent, perforin-based killing mechanism involving activation of TLR7 and signaling through Triggering Receptor-1 Expressed on Myeloid cells (TREM-1). This novel subpopulation of perforin-expressing imDCs was also detected in various lymphoid tissues in normal animals and its frequency was markedly enhanced after GM-CSF administration. |
| Databáze: | OpenAIRE |
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