Defective CD8 Signaling Pathways Delay Rejection in Older Recipients
Autor: | Felix Krenzien, Anke Jurisch, Christian Denecke, Hirofumi Uehara, Karoline Edtinger, Stefan G. Tullius, Markus Quante, Abdallah Elkhal, Xupeng Ge, X. Yuan, H. Li, D Bedi, Irene Kim, Guangxiang Liu |
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Rok vydání: | 2016 |
Předmět: |
Graft Rejection
0301 basic medicine Aging Time Factors T cell CD40 Ligand Cell Communication CD8-Positive T-Lymphocytes Biology Interferon-gamma 03 medical and health sciences Interleukin 21 0302 clinical medicine Phagocytosis Cell Movement medicine Animals Cytotoxic T cell IL-2 receptor Antigen-presenting cell Cells Cultured Chemokine CCL3 Homeodomain Proteins Mice Knockout Transplantation Gene Expression Profiling ZAP70 Graft Survival Age Factors Dendritic Cells Skin Transplantation Allografts Natural killer T cell Adoptive Transfer Interleukin-2 Receptor beta Subunit Mice Inbred C57BL Genes T-Cell Receptor 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Mice Inbred DBA Immunology Mice Inbred CBA Interleukin 12 Signal Transduction 030215 immunology |
Zdroj: | Transplantation. 100:69-79 |
ISSN: | 0041-1337 |
DOI: | 10.1097/tp.0000000000000886 |
Popis: | CD8+ T cells play a cardinal feature in response to alloantigens and are able to generate effector/memory T cells independently from CD4+ T cells. To investigate the impact of aging on CD8 T cells, we used a fully mismatched mouse skin transplant model. Our findings showed a prolonged allograft survival in older recipients associated with a significant increase of CD4+ and CD8+ CD44high CD62Llow effector/memory T cells and a reduced systemic IFNγ production. When reconstituting young CBA Rag-1 mice that lack mature T and B cells with old CD8+ T cells expressing clonal anti-H2K T cell receptor (TCR) alloreactive for MHC I, graft survival was significantly prolonged and comparable to those receiving young CD8+ T cells. Moreover, our data showed that reduced systemic IFNγ levels observed in old recipients had been linked to a compromised expression of the IL-2R β subunit (CD122) by old CD8+ T cells. In addition, we observed an impaired IFNγ production on IL-2 receptor activation. At the same time, gene profiling analysis of old CD8 T cells demonstrated reduced chemokine ligand-3 and CD40L expression that resulted in compromised CD8+ T cell/dendritic cell communication, leading to impaired migratory and phagocytic activity of CD11c cells.Collectively, our study demonstrated that aging delays allograft rejection. CD8 T cells play a critical role in this process linked to a compromised production of IFNγ, in addition to a defective IL-2 receptor signaling machinery and a defective communication between CD8 T cells and dendritic cells. |
Databáze: | OpenAIRE |
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