Donor bone marrow-derived dendritic cells prolong corneal allograft survival and promote an intragraft immunoregulatory milieu
| Autor: | Marese Cregg, Lisa O'Flynn, Oliver Treacy, Thomas Ritter, Lokesh Joshi, Maurice Morcos, Mikhail Nosov, Jared Q. Gerlach, Aideen E. Ryan |
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| Přispěvatelé: | ~|1267883|~ |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Graft Rejection
Male medicine.medical_treatment T-Lymphocytes Regulatory in-vivo Dexamethasone Corneal Transplantation Rats Sprague-Dawley Neovascularization 0302 clinical medicine Drug Discovery Medicine induction t-cells 0303 health sciences Graft Survival anti-cd4 monoclonal-antibody Immunosuppression Allografts Tissue Donors ido 3. Good health Cellular infiltration transplant tolerance Allogeneic Lymphocyte Molecular Medicine Original Article rejection medicine.symptom splenocyte infusions Allogeneic transplantation nitric-oxide Bone Marrow Cells 03 medical and health sciences Glucocorticoid-treated BMDCs Genetics Animals Transplantation Homologous Antigen-presenting cell Molecular Biology 030304 developmental biology Immunosuppression Therapy Pharmacology business.industry Organ transplantation Dendritic Cells medicine.disease Donor bone marrow-derived dendritic cells (BMDCs) Rats Transplantation Disease Models Animal Rats Inbred Lew Immunology ocular immune privilege business Ex vivo 030215 immunology |
| Popis: | Journal article Investigations into cell therapies for application in organ transplantation have grown. Here, we describe the ex vivo generation of donor bone marrow-derived dendritic cells (BMDCs) and glucocorticoid-treated BMDCs with potent immunomodulatory properties for application in allogeneic transplantation. BMDCs were treated with dexamethasone (Dexa) to induce an immature, maturation-resistant phenotype. BMDC and Dexa BMDC phenotype, antigen presenting cell function, and immunomodulatory properties were fully characterized. Both populations display significant immunomodulatory properties, including, but not limited to, a significant increase in mRNA expression of programmed death-ligand 1 and indoleamine 2,3-dioxygenase. BMDCs and Dexa BMDCs display a profound impaired capacity to stimulate allogeneic lymphocytes. Moreover, in a fully MHC I/II mismatched rat corneal transplantation model, injection of donor-derived, untreated BMDC or Dexa BMDCs (1â Ã â 10(6) cells, day -7) significantly prolonged corneal allograft survival without the need for additional immunosuppression. Although neovascularization was not reduced and evidence of donor-specific alloantibody response was detected, a significant reduction in allograft cellular infiltration combined with a significant increase in the ratio of intragraft FoxP3-expressing regulatory cells was observed. Our comprehensive analysis demonstrates the novel cellular therapeutic approach and significant effect of donor-derived, untreated BMDCs and Dexa BMDCs in preventing corneal allograft rejection. Science Foundation Ireland - Grant No. [07/IN.1/B925], 09/SRC-B1794; European Regional Development Fund peer-reviewed |
| Databáze: | OpenAIRE |
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