Both innate and adaptive major histocompatibility complex class I-dependent immunity impair long-term islet xenograft survival
| Autor: | F, Ramirez-Victorino, F, Ramirez-Victorio, J N, Beilke, R G, Gill |
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| Rok vydání: | 2008 |
| Předmět: |
Graft Rejection
Primates Swine Transplantation Heterologous Islets of Langerhans Transplantation chemical and pharmacologic phenomena CD8-Positive T-Lymphocytes Major histocompatibility complex Immune system Immunity MHC class I Cytotoxic T cell Animals Transplantation geography geography.geographical_feature_category biology Graft Survival Histocompatibility Antigens Class I Islet Natural killer T cell Immunity Innate Killer Cells Natural Tolerance induction Immunology biology.protein Surgery |
| Zdroj: | Transplantation proceedings. 40(2) |
| ISSN: | 0041-1345 |
| Popis: | Natural killer (NK) cells have long been appreciated for their rapid, proinflammatory contribution to host defense. However, more recent studies show an unexpected regulatory role for host major histocompatibility complex (MHC) class I-dependent immunity and NK cells in promoting tolerance induction to islet allografts. It is unclear whether the potential tolerance induction to islet xenografts follows similar requirements to those found in allograft tolerance. In this study, we determined whether induced islet xenograft prolongation also showed a reliance on MHC class I-dependent immune pathways. In particular, we tested whether NK1.1+ cells and/or CD8 T cells were required for the long-term islet xenograft survival in a rat-to-mouse transplant model. Short-term host treatment with combined anti-CD154 plus anti-LFA-1 (CD11a) resulted in prolonged, but not indefinite, survival of WF rat islet xenografts in C57BI/6 mouse recipients. In stark contrast with similar islet allograft studies, adjunct treatment with anti-NK1.1 therapy combined wither anti-CD154/anti-LFA-1 treatment led to long-term (>100 days) survival of the majority of islet xenografts. In parallel studies, we determined whether CD8 T cells also contributed a barrier to xenograft survival. Similar to results found in anti-NK1.1-treated animals, CD8-deficient (knockout) recipients also demonstrated augmented xenograft prolongation after combined anti-CD154/anti-LFA-1 therapy. Taken together, NK1.1+ cells (NK/NKT cells) and CD8 T cells constitute differing MHC class I-dependent immune pathways forming a significant barrier to xenograft prolongation. |
| Databáze: | OpenAIRE |
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