Interleukin‐7 receptor blockade by an anti‐ CD 127 monoclonal antibody in nonhuman primate kidney transplantation
Résumé
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.
Mots clés
animal models: nonhuman primate
basic (laboratory) research/science
cytokines/cytokine receptors
immunobiology
immunosuppressant ‐ fusion proteins and monoclonal antibodies: T cell specific
immunosuppression/immune modulation
kidney (allograft) function/ dysfunction
kidney transplantation/nephrology
lymphocyte biology
translational research/ science