Permanent Survival of Fully MHC-Mismatched Islet Allografts by Targeting a Single Chemokine Receptor Pathway
Autor: | Liqing Wang, Guoxiang Xiong, Aidan Hancock, Wayne W. Hancock, Michael D. Gunn, Iris Lee, Rongxiang Han |
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Rok vydání: | 2005 |
Předmět: |
Graft Rejection
Receptors CCR7 Chemokine T-Lymphocytes T cell Immunology Islets of Langerhans Transplantation C-C chemokine receptor type 7 Biology Lymphocyte Activation Major Histocompatibility Complex Mice Chemokine receptor medicine Animals Transplantation Homologous Immunology and Allergy B cell B-Lymphocytes Mice Inbred BALB C Chemokine CCL21 Graft Survival CCL19 Dendritic Cells Dendritic cell Mice Mutant Strains Mice Inbred C57BL medicine.anatomical_structure Mice Inbred DBA Chemokines CC biology.protein Chemokine CCL19 Heart Transplantation Receptors Chemokine Lymph Nodes CCL21 |
Zdroj: | The Journal of Immunology. 175:6311-6318 |
ISSN: | 1550-6606 0022-1767 |
DOI: | 10.4049/jimmunol.175.10.6311 |
Popis: | Chemokine receptor blockade can diminish the recruitment of host effector cells and prolong allograft survival, but little is known of the role of chemokine receptors in promoting host sensitization. We engrafted fully allogeneic islets into streptozotocin-treated normal mice or mice with the autosomal recessive paucity of lymph node T cell (plt) mutation; the latter lack secondary lymphoid expression of the CCR7 ligands, secondary lymphoid organ chemokine (CCL21) and EBV-induced molecule-1 ligand chemokine (CCL19). plt mice showed permanent survival of islets engrafted under the kidney capsule, whereas controls rejected islet allografts in 12 days (p < 0.001), and consistent with this, plt mice had normal allogeneic T cell responses, but deficient migration of donor dendritic cell to draining lymph nodes. Peritransplant i.v. injection of donor splenocytes caused plt recipients to reject their allografts by 12 days, and sensitization at 60 days posttransplant of plt mice with well-functioning allografts restored acute rejection. Finally, islet allografts transplanted intrahepatically in plt mice were rejected ∼12 days posttransplant, like controls, as were primarily revascularized cardiac allografts. These data show that the chemokine-directed homing of donor dendritic cell to secondary lymphoid tissues is essential for host sensitization and allograft rejection. Interruption of such homing can prevent T cell priming and islet allograft rejection despite normal T and B cell functions of the recipient, with potential clinical implications. |
Databáze: | OpenAIRE |
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