دورية أكاديمية
Regulatory CD8 T cells that recognize Qa-1 expressed by CD4 T-helper cells inhibit rejection of heart allografts.
| العنوان: | Regulatory CD8 T cells that recognize Qa-1 expressed by CD4 T-helper cells inhibit rejection of heart allografts. |
|---|---|
| المؤلفون: | Choi JY; Division of Renal Medicine, Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115., Eskandari SK; Division of Renal Medicine, Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.; Division of Nephrology, University Medical Center Groningen, University of Groningen, 9700 AB Groningen, The Netherlands., Cai S; Division of Renal Medicine, Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115., Sulkaj I; Division of Renal Medicine, Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115., Assaker JP; Division of Renal Medicine, Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115., Allos H; Division of Renal Medicine, Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115., AlHaddad J; Division of Renal Medicine, Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115., Muhsin SA; Division of Renal Medicine, Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115., Alhussain E; Division of Renal Medicine, Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115., Mansouri A; Division of Renal Medicine, Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115., Yeung MY; Division of Renal Medicine, Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115., Seelen MAJ; Division of Nephrology, University Medical Center Groningen, University of Groningen, 9700 AB Groningen, The Netherlands., Kim HJ; Department of Cancer Immunology & Virology, Dana-Farber Cancer Institute, Boston, MA 02215.; Department of Immunology, Harvard Medical School, Boston, MA 02115., Cantor H; Department of Cancer Immunology & Virology, Dana-Farber Cancer Institute, Boston, MA 02215; harvey_cantor@dfci.harvard.edu Jazzi@bwh.harvard.edu.; Department of Immunology, Harvard Medical School, Boston, MA 02115., Azzi JR; Division of Renal Medicine, Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115; harvey_cantor@dfci.harvard.edu Jazzi@bwh.harvard.edu. |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Mar 17; Vol. 117 (11), pp. 6042-6046. Date of Electronic Publication: 2020 Feb 28. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| 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: | Graft Rejection/*immunology , Heart Transplantation/*adverse effects , Histocompatibility Antigens Class I/*immunology , T-Lymphocytes, Helper-Inducer/*metabolism , T-Lymphocytes, Regulatory/*immunology, Allografts/immunology ; Allografts/metabolism ; Animals ; Disease Models, Animal ; Graft Rejection/blood ; Graft Rejection/genetics ; Graft Survival/immunology ; Histocompatibility Antigens Class I/genetics ; Histocompatibility Antigens Class I/metabolism ; Humans ; Immune Tolerance ; Isoantibodies/immunology ; Isoantibodies/metabolism ; Isoantigens/immunology ; Isoantigens/metabolism ; Mice ; Myocardium/immunology ; Myocardium/metabolism ; Point Mutation ; Receptors, Antigen, T-Cell/immunology ; Receptors, Antigen, T-Cell/metabolism ; T-Lymphocytes, Helper-Inducer/immunology ; Transplantation, Homologous/adverse effects |
| مستخلص: | Induction of longstanding immunologic tolerance is essential for survival of transplanted organs and tissues. Despite recent advances in immunosuppression protocols, allograft damage inflicted by antibody specific for donor organs continues to represent a major obstacle to graft survival. Here we report that activation of regulatory CD8 T cells (CD8 Treg) that recognize the Qa-1 class Ib major histocompatibility complex (MHC), a mouse homolog of human leukocyte antigen-E (HLA-E), inhibits antibody-mediated immune rejection of heart allografts. We analyzed this response using a mouse model that harbors a point mutation in the class Ib MHC molecule Qa-1, which disrupts Qa-1 binding to the T cell receptor (TCR)-CD8 complex and impairs the CD8 Treg response. Despite administration of cytotoxic T lymphocyte antigen 4 (CTLA-4) immunoglobulin (Ig), Qa-1 mutant mice developed robust donor-specific antibody responses and accelerated heart graft rejection. We show that these allo-antibody responses reflect diminished Qa-1-restricted CD8 Treg-mediated suppression of host follicular helper T cell-dependent antibody production. These findings underscore the critical contribution of this Qa-1/HLA-E-dependent regulatory pathway to maintenance of transplanted organs and suggest therapeutic approaches to ameliorate allograft rejection. Competing Interests: The authors declare no competing interest. |
| References: | Immunity. 2007 May;26(5):593-604. (PMID: 17509909) J Immunol. 2007 Oct 15;179(8):5099-108. (PMID: 17911595) J Immunol Res. 2016;2016:1910852. (PMID: 27493971) Transplantation. 1973 Oct;16(4):343-50. (PMID: 4583148) N Engl J Med. 2018 Sep 20;379(12):1150-1160. (PMID: 30231232) Cell Rep. 2018 Aug 21;24(8):1967-1976.e4. (PMID: 30134159) Adv Immunol. 2018;140:1-20. (PMID: 30366517) Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19420-5. (PMID: 19047627) Transplantation. 2016 May;100(5):1032-40. (PMID: 26845308) J Clin Invest. 2013 Mar;123(3):1382-9. (PMID: 23376792) Immunobiology. 2017 Mar;222(3):536-543. (PMID: 27871782) J Heart Lung Transplant. 2013 Dec;32(12):1147-62. (PMID: 24263017) Proc Natl Acad Sci U S A. 2013 Dec 24;110(52):21089-94. (PMID: 24324159) Nature. 2019 Aug;572(7770):481-487. (PMID: 31391585) Transplantation. 2016 Aug;100(8):1683-91. (PMID: 27362308) Annu Rev Immunol. 2016 May 20;34:335-68. (PMID: 26907215) Proc Natl Acad Sci U S A. 2016 Dec 27;113(52):E8425-E8432. (PMID: 27956634) Nature. 2010 Sep 16;467(7313):328-32. (PMID: 20844537) Cell. 2018 Dec 13;175(7):1744-1755.e15. (PMID: 30503208) Cancer Immunol Res. 2014 Mar;2(3):207-16. (PMID: 24778317) BMC Immunol. 2017 Dec 19;18(1):52. (PMID: 29258420) J Biol Chem. 2003 Feb 14;278(7):5082-90. (PMID: 12411439) |
| معلومات مُعتمدة: | R01 AI048125 United States AI NIAID NIH HHS; R01 AI037562 United States AI NIAID NIH HHS; R01 AI134842 United States AI NIAID NIH HHS; T32 DK007527 United States DK NIDDK NIH HHS; T32 EB016652 United States EB NIBIB NIH HHS |
| فهرسة مساهمة: | Keywords: Ab-mediated rejection; CD8 Treg; HLA-E; Qa-1; follicular helper T cell |
| المشرفين على المادة: | 0 (Histocompatibility Antigens Class I) 0 (Isoantibodies) 0 (Isoantigens) 0 (Q surface antigens) 0 (Receptors, Antigen, T-Cell) |
| تواريخ الأحداث: | Date Created: 20200301 Date Completed: 20200713 Latest Revision: 20200829 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC7084119 |
| DOI: | 10.1073/pnas.1918950117 |
| PMID: | 32111690 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1091-6490 |
|---|---|
| DOI: | 10.1073/pnas.1918950117 |