دورية أكاديمية
أعرض في EDS

Resilience of T cell-intrinsic dysfunction in transplantation tolerance.

التفاصيل البيبلوغرافية
العنوان: Resilience of T cell-intrinsic dysfunction in transplantation tolerance.
المؤلفون: Miller ML; Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL 60637., McIntosh CM; Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL 60637., Wang Y; Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL 60637., Chen L; Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL 60637., Wang P; Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL 60637., Lei YM; Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL 60637., Daniels MD; Department of Surgery, Section of Transplantation, The University of Chicago, Chicago, IL 60637., Watkins E; Institute for Molecular Engineering, The University of Chicago, Chicago, IL 60637., Mora Solano C; Department of Surgery, Section of Transplantation, The University of Chicago, Chicago, IL 60637., Chong AS; Department of Surgery, Section of Transplantation, The University of Chicago, Chicago, IL 60637., Alegre ML; Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL 60637; malegre@midway.uchicago.edu.
المصدر: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2019 Nov 19; Vol. 116 (47), pp. 23682-23690. Date of Electronic Publication: 2019 Nov 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: Transplantation Immunology*, Graft Survival/*immunology , Immune Tolerance/*immunology , T-Lymphocyte Subsets/*immunology, Allografts ; Animals ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/transplantation ; Forkhead Transcription Factors/analysis ; Genes, Reporter ; Graft Rejection/immunology ; H-2 Antigens/immunology ; Heart Transplantation ; Histocompatibility Antigens Class II/immunology ; Immunologic Memory ; Isoantigens/immunology ; Listeria monocytogenes ; Listeriosis/immunology ; Lymphocyte Transfusion ; Mice ; Mice, Congenic ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Postoperative Complications/immunology ; T-Lymphocytes, Regulatory/immunology ; Tissue Donors
مستخلص: Following antigen stimulation, naïve T cells differentiate into memory cells that mediate antigen clearance more efficiently upon repeat encounter. Donor-specific tolerance can be achieved in a subset of transplant recipients, but some of these grafts are rejected after years of stability, often following infections. Whether T cell memory can develop from a tolerant state and whether these formerly tolerant patients develop antidonor memory is not known. Using a mouse model of cardiac transplantation in which donor-specific tolerance is induced with costimulation blockade (CoB) plus donor-specific transfusion (DST), we have previously shown that systemic infection with Listeria monocytogenes (Lm) months after transplantation can erode or transiently abrogate established tolerance. In this study, we tracked donor-reactive T cells to investigate whether memory can be induced when alloreactive T cells are activated in the setting of tolerance. We show alloreactive T cells persist after induction of cardiac transplantation tolerance, but fail to acquire a memory phenotype despite becoming antigen experienced. Instead, donor-reactive T cells develop T cell-intrinsic dysfunction evidenced when removed from the tolerant environment. Notably, Lm infection after tolerance did not rescue alloreactive T cell memory differentiation or functionality. CoB and antigen persistence were sufficient together but not separately to achieve alloreactive T cell dysfunction, and conventional immunosuppression could substitute for CoB. Antigen persistence was required, as early but not late surgical allograft removal precluded the acquisition of T cell dysfunction. Our results demonstrate transplant tolerance-associated T cell-intrinsic dysfunction that is resistant to memory development even after Lm-mediated disruption of tolerance.
Competing Interests: The authors declare no competing interest.
References: Nat Commun. 2015 Jul 07;6:7566. (PMID: 26151823)
Eur J Immunol. 2015 Jul;45(7):2017-27. (PMID: 25944401)
J Leukoc Biol. 2017 Apr;101(4):975-987. (PMID: 27810945)
Am J Transplant. 2019 Sep;19(9):2421-2433. (PMID: 30947382)
JCI Insight. 2018 Nov 15;3(22):. (PMID: 30429370)
J Clin Invest. 2003 Jun;111(12):1887-95. (PMID: 12813024)
Immunity. 2017 Dec 19;47(6):1114-1128.e6. (PMID: 29221730)
Nat Med. 2004 Jan;10(1):87-92. (PMID: 14647496)
Am J Transplant. 2017 Jan;17(1):81-90. (PMID: 27273890)
Am J Transplant. 2017 Sep;17(9):2350-2362. (PMID: 28502091)
Nat Immunol. 2006 Jun;7(6):652-62. (PMID: 16633346)
Am J Transplant. 2014 Jul;14(7):1599-611. (PMID: 24903438)
Curr Opin Organ Transplant. 2010 Aug;15(4):405-10. (PMID: 20616729)
Blood. 2009 Aug 20;114(8):1537-44. (PMID: 19423728)
J Exp Med. 2015 Jun 29;212(7):1125-37. (PMID: 26034050)
J Virol. 2012 Aug;86(15):8161-70. (PMID: 22623779)
J Exp Med. 1998 Dec 21;188(12):2205-13. (PMID: 9858507)
Am J Transplant. 2016 Oct;16(10):2842-2853. (PMID: 27063351)
Cell Rep. 2016 Feb 9;14(5):1232-1245. (PMID: 26804905)
Blood Adv. 2018 Mar 27;2(6):669-680. (PMID: 29563123)
J Exp Med. 1987 Feb 1;165(2):302-19. (PMID: 3029267)
Science. 2012 Feb 10;335(6069):723-7. (PMID: 22267581)
J Immunol. 2002 Nov 15;169(10):5387-91. (PMID: 12421910)
Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20701-6. (PMID: 22143783)
J Immunol. 2009 May 15;182(10):6217-25. (PMID: 19414775)
Am J Transplant. 2012 Dec;12(12):3296-307. (PMID: 22974211)
J Immunol. 2005 Jul 15;175(2):771-9. (PMID: 16002673)
N Engl J Med. 2007 Dec 20;357(25):2601-14. (PMID: 18094380)
Nat Immunol. 2003 Dec;4(12):1191-8. (PMID: 14625547)
Immunity. 2007 Oct;27(4):670-84. (PMID: 17950003)
Transplantation. 1973 Oct;16(4):343-50. (PMID: 4583148)
J Virol. 2000 Mar;74(5):2210-8. (PMID: 10666251)
Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):14602-7. (PMID: 21873213)
Cell Rep. 2018 Aug 21;24(8):2112-2126. (PMID: 30134172)
Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19954-9. (PMID: 18042727)
Nat Rev Immunol. 2015 Aug;15(8):486-99. (PMID: 26205583)
Front Immunol. 2015 Sep 08;6:456. (PMID: 26441961)
Am J Transplant. 2001 May;1(1):38-46. (PMID: 12095035)
J Immunol. 2003 Jan 1;170(1):477-86. (PMID: 12496434)
Am J Transplant. 2015 Dec;15(12):3055-66. (PMID: 26190648)
Immunology. 2013 Jul;139(3):277-84. (PMID: 23347146)
Am J Transplant. 2010 Jul;10(7):1524-33. (PMID: 20642679)
Am J Transplant. 2016 Oct;16(10):2854-2864. (PMID: 27091509)
Blood. 2003 Sep 1;102(5):1920-6. (PMID: 12750162)
Am J Transplant. 2017 Sep;17(9):2285-2299. (PMID: 28502128)
J Immunol. 2009 Mar 1;182(5):3032-8. (PMID: 19234199)
Science. 2016 Dec 2;354(6316):1160-1165. (PMID: 27789795)
Hepatology. 2013 Nov;58(5):1824-35. (PMID: 23532679)
Sci Transl Med. 2015 Jan 28;7(272):272ra10. (PMID: 25632034)
Proc Natl Acad Sci U S A. 2009 May 26;106(21):8623-8. (PMID: 19433785)
Front Immunol. 2018 Jun 20;9:1385. (PMID: 29973932)
Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):12145-50. (PMID: 25092331)
Curr Transplant Rep. 2014 Sep 1;1(3):137-146. (PMID: 25435071)
Am J Transplant. 2019 Mar;19(3):884-893. (PMID: 30468559)
J Immunol. 2008 May 1;180(9):5991-9. (PMID: 18424719)
معلومات مُعتمدة: P01 AI097113 United States AI NIAID NIH HHS; T32 HD007009 United States HD NICHD NIH HHS; T32 HL007237 United States HL NHLBI NIH HHS; 56006772 United States HHMI Howard Hughes Medical Institute
فهرسة مساهمة: Keywords: T cells; exhaustion; memory; tolerance; transplantation
المشرفين على المادة: 0 (Forkhead Transcription Factors)
0 (Foxp3 protein, mouse)
0 (H-2 Antigens)
0 (H-2K(K) antigen)
0 (Histocompatibility Antigens Class II)
0 (I-A(b) antigen, mouse)
0 (Isoantigens)
تواريخ الأحداث: Date Created: 20191106 Date Completed: 20200420 Latest Revision: 20210110
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC6876241
DOI: 10.1073/pnas.1910298116
PMID: 31685610
قاعدة البيانات: MEDLINE
الوصف
تدمد:1091-6490
DOI:10.1073/pnas.1910298116