Myeloid-derived suppressor cells increase and inhibit donor-reactive T cell responses to graft intestinal epithelium in intestinal transplant patients
| Autor: | Kareem Abu-Elmagd, Koji Hashimoto, Ajai Khanna, William M. Baldwin, Masato Fujiki, Karen Keslar, Shinji Okano, Hiroto Kayashima, Guilherme Costa, Mohammed Osman, Danielle D. Kish, Charles Miller, John J. Fung, Robert L. Fairchild |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Graft Rejection Chemokine T cell T-Lymphocytes Peripheral blood mononuclear cell Article 03 medical and health sciences 0302 clinical medicine Intestinal mucosa Isoantibodies medicine Immunology and Allergy Humans Pharmacology (medical) Intestinal Mucosa Cells Cultured Transplantation biology business.industry Myeloid-Derived Suppressor Cells Graft Survival Interleukin HLA-DR Antigens Organ Transplantation Prognosis Intestinal epithelium Tissue Donors 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research Myeloid-derived Suppressor Cell biology.protein Leukocytes Mononuclear Bone marrow business Follow-Up Studies |
| Zdroj: | American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 18(10) |
| ISSN: | 1600-6143 |
| Popis: | Recent advances in immunosuppressive regimens have decreased acute cellular rejection (ACR) rates and improved intestinal transplant (ITx) recipient survival. We investigated the role of myeloid-derived suppressor cells (MDSCs) in ITx. We identified MDSCs as CD33(+)CD11b(+)lineage(CD3/CD56/CD19)(−)HLA-DR(−/low) cells with 3 subsets, CD14(−)CD15(−) (e-MDSC), CD14(+)CD15(−) (M-MDSC), and CD14(−)CD15(+) (PMN-MDSC), in peripheral blood mononuclear cells (PBMCs) and mononuclear cells in the grafted intestinal mucosa. Total MDSC numbers increased in PBMCs following ITx; among MDSC subsets, M-MDSC numbers were maintained at high level after 2 months following ITx. The MDSC numbers decreased in ITx recipients suffering from ACR. MDSC numbers were positively correlated with serum IL-6 levels and the glucocorticoid administration index. IL-6 and methylprednisolone enhanced the differentiation of bone marrow cells (BMCs) to MDSCs in vitro. M-MDSCs and e-MDSCs expressed CCR1, -2, and -3, e-MDSCs and PMN-MDSCs expressed CXCR2, and intestinal grafts expressed the corresponding chemokine ligands following ITx. Of note, the percentage of MDSCs among intestinal mucosal CD45(+) cells increased after ITx. A novel in vitro assay demonstrated that MDSCs suppressed donor-reactive T-cell-mediated destruction of donor intestinal epithelial organoids. Taken together, our results suggest that MDSCs accumulate in the recipient PBMCs and the grafted intestinal mucosa in ITx, and may regulate ACR. |
| Databáze: | OpenAIRE |
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