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. |
References: | Immunity. 2013 Jan 24;38(1):140-52. (PMID: 23260194) Annu Rev Immunol. 2008;26:677-704. (PMID: 18173375) Immunity. 2013 Jan 24;38(1):5-7. (PMID: 23352218) J Heart Lung Transplant. 2006 May;25(5):550-6. (PMID: 16678034) Transplant Proc. 1998 Jun;30(4):1027-8. (PMID: 9636414) J Heart Lung Transplant. 1998 Oct;17(10):1007-16. (PMID: 9811410) Eur J Immunol. 2005 Mar;35(3):738-45. (PMID: 15724249) Clin Transplant. 2011 Sep-Oct;25(5):766-75. (PMID: 21114535) Cell. 1996 Aug 23;86(4):643-53. (PMID: 8752218) Immunity. 2013 Jan 24;38(1):131-9. (PMID: 23260193) J Immunol. 2002 Feb 15;168(4):1682-9. (PMID: 11823497) J Immunol. 2005 Mar 15;174(6):3741-8. (PMID: 15749914) Curr Atheroscler Rep. 2006 Mar;8(2):119-30. (PMID: 16510046) Annu Rev Pathol. 2009;4:19-47. (PMID: 18717641) Nat Chem Biol. 2012 Jul;8(7):661-8. (PMID: 22683610) Nature. 2006 Feb 9;439(7077):682-7. (PMID: 16382236) J Immunol. 2008 Oct 1;181(7):4832-9. (PMID: 18802087) Nat Immunol. 2011 Jun;12(6):492-9. (PMID: 21739672) Nat Rev Immunol. 2004 May;4(5):325-35. (PMID: 15122198) Transplantation. 2010 Nov 15;90(9):935-44. (PMID: 20703180) J Leukoc Biol. 2002 Feb;71(2):311-8. (PMID: 11818453) J Am Soc Nephrol. 2004 Nov;15(11):2893-901. (PMID: 15504942) Am J Transplant. 2012 Oct;12(10):2575-87. (PMID: 22900886) J Heart Lung Transplant. 2001 Mar;20(3):340-9. (PMID: 11257561) Transplantation. 1973 Oct;16(4):343-50. (PMID: 4583148) Am J Transplant. 2011 Mar;11(3):439-49. (PMID: 21342445) Circulation. 1997 Jan 7;95(1):191-6. (PMID: 8994436) Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14733-8. (PMID: 20679213) J Exp Med. 2003 Jul 7;198(1):63-9. (PMID: 12847137) Blood. 1997 Dec 1;90(11):4459-72. (PMID: 9373256) Am J Transplant. 2011 Apr;11(4):786-97. (PMID: 21401865) Immunity. 2001 Apr;14(4):387-97. (PMID: 11336684) J Immunol. 1997 Jun 1;158(11):5191-9. (PMID: 9164936) J Am Soc Nephrol. 2007 Nov;18(11):2929-36. (PMID: 17928506) Lancet. 2011 Oct 15;378(9800):1428-37. (PMID: 22000139) J Exp Med. 2008 Dec 22;205(13):3133-44. (PMID: 19047438) PLoS Pathog. 2010 Jun 10;6(6):e1000947. (PMID: 20548953) J Immunol. 2002 Feb 15;168(4):1934-9. (PMID: 11823529) |
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 |