دورية أكاديمية
Impaired selectin-dependent leukocyte recruitment induces T-cell exhaustion and prevents chronic allograft vasculopathy and rejection.
| العنوان: | Impaired selectin-dependent leukocyte recruitment induces T-cell exhaustion and prevents chronic allograft vasculopathy and rejection. |
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| المؤلفون: | Sarraj B; Division of Nephrology, Department of Medicine,Division of Organ Transplantation, Department of Surgery, and., Ye J; Division of Organ Transplantation, Department of Surgery, andDepartment of Kidney Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China., Akl AI; Division of Nephrology, Department of Medicine., Chen G; Division of Organ Transplantation, Department of Surgery, and., Wang JJ; Division of Organ Transplantation, Department of Surgery, and., Zhang Z; Division of Organ Transplantation, Department of Surgery, and., Abadja F; Division of Organ Transplantation, Department of Surgery, and., Abecassis M; Division of Organ Transplantation, Department of Surgery, and., Miller SD; Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611; and., Kansas GS; Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611; and., Ansari MJ; Division of Nephrology, Department of Medicine,Division of Organ Transplantation, Department of Surgery, and jansari@northwestern.edu. |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2014 Aug 19; Vol. 111 (33), pp. 12145-50. Date of Electronic Publication: 2014 Aug 04. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : National Academy of Sciences |
| مواضيع طبية MeSH: | Allografts* , Graft Rejection*, Blood Vessels/*pathology , CD4-Positive T-Lymphocytes/*immunology , Leukocytes/*cytology , Selectins/*physiology, Adoptive Transfer ; Cell Movement ; Flow Cytometry ; Fucosyltransferases/genetics ; Humans |
| مستخلص: | Selectin-selectin ligand interactions mediate the initial steps in leukocyte migration, an integral part of immune responses. Fucosyltransferase-VII (FucT-VII), encoded by Fut7, is essential for biosynthesis of selectin ligands. In an established model of cardiac allograft vasculopathy and chronic rejection, Fut7(-/-) recipients exhibited long-term graft survival with minimal vasculopathy compared with WT controls. Graft survival was associated with CD4 T-cell exhaustion in the periphery, characterized by impaired effector cytokine production, defective proliferation, increased expression of inhibitory receptors programmed death-1 (PD-1) and T cell Ig- and mucin-domain-containing molecule-3 (Tim-3), low levels of IL-7Rα on CD4 T cells, and reduced migration of polyfunctional CD4 memory T cells to the allograft. Blocking PD-1 triggered rejection only in Fut7(-/-) recipients, whereas depleting regulatory T cells had no effect in either Fut7(-/-) or WT recipients. Adoptive transfer experiments confirmed that this CD4 T cell-exhausted phenotype is seen primarily in Fut7(-/-) CD4 T cells. These data suggest that impaired leukocyte recruitment is a novel mechanism leading to CD4 T-cell exhaustion. Our experimental system serves as an excellent model to study CD4 T-cell exhaustion as a dominant mechanism of transplant tolerance. Further, targeting FucT-VII may serve as a promising strategy to prevent chronic allograft rejection and promote tolerance. |
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| معلومات مُعتمدة: | K08 AI080836 United States AI NIAID NIH HHS; P30 CA060553 United States CA NCI NIH HHS; R01 NS026543 United States NS NINDS NIH HHS |
| فهرسة مساهمة: | Keywords: adhesion; apoptosis; traffic |
| المشرفين على المادة: | 0 (Selectins) EC 2.4.1.- (FUT7 protein, human) EC 2.4.1.- (Fucosyltransferases) |
| تواريخ الأحداث: | Date Created: 20140806 Date Completed: 20141103 Latest Revision: 20211021 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC4143062 |
| DOI: | 10.1073/pnas.1303676111 |
| PMID: | 25092331 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1091-6490 |
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| DOI: | 10.1073/pnas.1303676111 |