التفاصيل البيبلوغرافية
| العنوان: |
IL-6 inhibition prevents costimulation blockade-resistant allograft rejection in T cell-depleted recipients by promoting intragraft immune regulation in mice. |
| المؤلفون: |
Muckenhuber, Moritz, Mengrelis, Konstantinos, Weijler, Anna Marianne, Steiner, Romy, Kainz, Verena, Buresch, Marlena, Regele, Heinz, Derdak, Sophia, Kubetz, Anna, Wekerle, Thomas |
| المصدر: |
Nature Communications; 6/3/2024, Vol. 15 Issue 1, p1-16, 16p |
| مصطلحات موضوعية: |
T cells, GRAFT rejection, REGULATORY T cells, INTERLEUKIN-6, HEART transplantation, CHIMERIC proteins |
| مستخلص: |
The efficacy of costimulation blockade with CTLA4-Ig (belatacept) in transplantation is limited due to T cell-mediated rejection, which also persists after induction with anti-thymocyte globulin (ATG). Here, we investigate why ATG fails to prevent costimulation blockade-resistant rejection and how this barrier can be overcome. ATG did not prevent graft rejection in a murine heart transplant model of CTLA4-Ig therapy and induced a pro-inflammatory cytokine environment. While ATG improved the balance between regulatory T cells (Treg) and effector T cells in the spleen, it had no such effect within cardiac allografts. Neutralizing IL-6 alleviated graft inflammation, increased intragraft Treg frequencies, and enhanced intragraft IL-10 and Th2-cytokine expression. IL-6 blockade together with ATG allowed CTLA4-Ig therapy to achieve long-term, rejection-free heart allograft survival. This beneficial effect was abolished upon Treg depletion. Combining ATG with IL-6 blockade prevents costimulation blockade-resistant rejection, thereby eliminating a major impediment to clinical use of costimulation blockers in transplantation. The use of CTLA4-Ig fusion proteins in transplantation remains limited due to co-stimulation blockade-resistant rejection (CBRR). In this study, the authors demonstrate that IL-6 blockade reduces CBRR in murine cardiac transplants in the context of T cell-depleting induction regimens and CTLA4-Ig treatment. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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