Interleukin-7 receptor blockade by an anti-CD127 monoclonal antibody in nonhuman primate kidney transplantation.
Am J Transplant
; 20(1): 101-111, 2020 01.
Article
em En
| MEDLINE
| ID: mdl-31344323
ABSTRACT
IL-7 is an important cytokine for T cell lymphopoiesis. Blockade of the IL-7 signaling pathway has been shown to induce long-term graft survival or graft tolerance in murine transplant models through inhibiting T cell homeostasis and favoring immunoregulation. 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 receptor 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 limiting factor for T cell homeostasis in primates.
Palavras-chave
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
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Depleção Linfocítica
/
Transplante de Rim
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Receptores de Interleucina-7
/
Subunidade alfa de Receptor de Interleucina-7
/
Rejeição de Enxerto
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Sobrevivência de Enxerto
/
Anticorpos Monoclonais
Tipo de estudo:
Etiology_studies
/
Guideline
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article