Interleukin‐7 receptor blockade by an anti‐ CD 127 monoclonal antibody in nonhuman primate kidney transplantation

Abstract : IL‐7 is an important cytokine for T cell lymphopoiesis. Blockade of the IL‐7 signal‐ing pathway has been shown to induce long‐term graft survival or graft tolerance in murine transplant models through inhibiting T cell homeostasis and favoring im ‐munoregulation. In this study, we assessed for the first time the effects of a blocking anti‐human cluster of differentiation 127 (CD127) mAb administered in combination with low‐dose tacrolimus or thymoglobulin in a life‐sustaining kidney allograft model in baboons. Contrary to our expectation, the addition of an anti‐CD127 mAb to the treatment protocols did not prolong graft survival compared to low‐dose tacrolimus alone or thymoglobulin alone. Anti‐CD127 mAb administration led to full CD127 re ‐ceptor occupancy during the follow‐up period. However, all treated animals lost their kidney graft between 1 week and 2 weeks after transplantation. Unlike in rodents, in nonhuman primates, anti‐CD127 mAb treatment does not decrease the absolute numbers of lymphocyte and lymphocyte subsets and does not effectively inhibit postdepletional T cell proliferation and homeostasis, suggesting that IL‐7 is not a lim ‐iting factor for T cell homeostasis in primates.
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Contributor : Ana Paula Dutra Azevedo <>
Submitted on : Tuesday, October 29, 2019 - 12:00:31 PM
Last modification on : Wednesday, October 30, 2019 - 1:28:02 AM

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Hoa Le Mai, Thi van Ha Nguyen, Julien Branchereau, Nicolas Poirier, Karine Renaudin, et al.. Interleukin‐7 receptor blockade by an anti‐ CD 127 monoclonal antibody in nonhuman primate kidney transplantation. American Journal of Transplantation, Wiley, 2019, ⟨10.1111/ajt.15543⟩. ⟨inserm-02337117⟩

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