دورية أكاديمية
Treg-mediated prolonged survival of skin allografts without immunosuppression.
| العنوان: | Treg-mediated prolonged survival of skin allografts without immunosuppression. |
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| المؤلفون: | Pilat N; Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.; St Vincent's Clinical School, University of New South Wales, Sydney, NSW 2010, Australia.; Department of Surgery, Medical University of Vienna, 1090 Vienna, Austria., Wiletel M; Department of Surgery, Medical University of Vienna, 1090 Vienna, Austria., Weijler AM; Department of Surgery, Medical University of Vienna, 1090 Vienna, Austria., Steiner R; Department of Surgery, Medical University of Vienna, 1090 Vienna, Austria., Mahr B; Department of Surgery, Medical University of Vienna, 1090 Vienna, Austria., Warren J; Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.; St Vincent's Clinical School, University of New South Wales, Sydney, NSW 2010, Australia., Corpuz TM; Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.; St Vincent's Clinical School, University of New South Wales, Sydney, NSW 2010, Australia., Wekerle T; Department of Surgery, Medical University of Vienna, 1090 Vienna, Austria., Webster KE; Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.; St Vincent's Clinical School, University of New South Wales, Sydney, NSW 2010, Australia., Sprent J; Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; j.sprent@garvan.org.au.; St Vincent's Clinical School, University of New South Wales, Sydney, NSW 2010, Australia. |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2019 Jul 02; Vol. 116 (27), pp. 13508-13516. Date of Electronic Publication: 2019 Jun 13. |
| نوع المنشور: | Journal Article; 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: | Graft Survival*/immunology , Skin Transplantation*, Graft Rejection/*prevention & control , T-Lymphocytes, Regulatory/*immunology, Allografts ; Animals ; Antibodies, Monoclonal/immunology ; Female ; Flow Cytometry ; Immunosuppressive Agents/therapeutic use ; Interleukin-2/immunology ; Interleukin-6/antagonists & inhibitors ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Sirolimus/therapeutic use |
| مستخلص: | Injection of Interleukin-2 (IL-2) complexed with a particular anti-IL-2 monoclonal antibody (mab) JES6-1 has been shown to selectively expand CD4 + Foxp3 + T regulatory T cells (Tregs) in vivo. Although the potency of this approach with regard to transplantation has already been proven in an islet transplantation model, skin graft survival could not be prolonged. Since the latter is relevant to human allograft survival, we sought to improve the efficiency of IL-2 complex (cplx) treatment for skin allograft survival in a stringent murine skin graft model. Here, we show that combining low doses of IL-2 cplxs with rapamycin and blockade of the inflammatory cytokine IL-6 leads to long-term (>75 d) survival of major histocompatibility complex-different skin allografts without the need for immunosuppression. Allograft survival was critically dependent on CD25 + FoxP3 + Tregs and was not accompanied by impaired responsiveness toward donor alloantigens in vitro after IL-2 cplx treatment was stopped. Furthermore, second donor-type skin grafts were rejected and provoked rejection of the primary graft, suggesting that operational tolerance is not systemic but restricted to the graft. These findings plus the lack of donor-specific antibody formation imply that prolonged graft survival was largely a reflection of immunological ignorance. The results may represent a potentially clinically translatable strategy for the development of protocols for tolerance induction. Competing Interests: The authors declare no conflict of interest. |
| التعليقات: | Erratum in: Proc Natl Acad Sci U S A. 2020 May 5;117(18):10097. (PMID: 32366648) |
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| معلومات مُعتمدة: | P 31186 Austria FWF_ Austrian Science Fund FWF |
| فهرسة مساهمة: | Keywords: interleukin-2; regulatory T cells; tolerance; transplantation |
| المشرفين على المادة: | 0 (Antibodies, Monoclonal) 0 (Immunosuppressive Agents) 0 (Interleukin-2) 0 (Interleukin-6) W36ZG6FT64 (Sirolimus) |
| تواريخ الأحداث: | Date Created: 20190615 Date Completed: 20200330 Latest Revision: 20230201 |
| رمز التحديث: | 20230201 |
| مُعرف محوري في PubMed: | PMC6613183 |
| DOI: | 10.1073/pnas.1903165116 |
| PMID: | 31196957 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1091-6490 |
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| DOI: | 10.1073/pnas.1903165116 |