Interleukin-7 receptor blockade by an anti-CD127 monoclonal antibody in nonhuman primate kidney transplantation

Autor: Thi Van Ha Nguyen, Jeremy Hervouet, Hoa Le Mai, Nicolas Poirier, Jean-Paul Soulillou, David Minault, Julien Branchereau, Gilles Blancho, Caroline Mary, Karine Renaudin, Lyssia Belarif, Sophie Brouard, Bernard Vanhove, Stéphanie Le Bas-Berdardet
Přispěvatelé: Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Immunotherapy in Transplantation And Autoimmunity (Team 3 - U1064 Inserm - CRTI), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Service d'urologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), OSE Immunotherapeutics [Nantes, France], Service d'Anatomie Pathologique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre Hospitalier Universitaire G. R. Laennec (HGRL Saint-Herblain), Fondation pour la Recherche Médicale, Le Bihan, Sylvie
Rok vydání: 2020
Předmět:
basic (laboratory) research/science
Graft Rejection
[SDV]Life Sciences [q-bio]
Lymphocyte
medicine.medical_treatment
T cell
kidney transplantation/nephrology
chemical and pharmacologic phenomena
immunosuppression/immune modulation
030230 surgery
Lymphocyte Depletion
Interleukin-7 Receptor alpha Subunit
03 medical and health sciences
Postoperative Complications
0302 clinical medicine
immunosuppressant ‐ fusion proteins and monoclonal antibodies: T cell specific
kidney (allograft) function/ dysfunction
medicine
Animals
Immunology and Allergy
Pharmacology (medical)
Lymphopoiesis
immunobiology
translational research/ science
030304 developmental biology
0303 health sciences
Transplantation
Receptors
Interleukin-7
Cluster of differentiation
Thymoglobulin
business.industry
Graft Survival
Antibodies
Monoclonal
Kidney Transplantation
lymphocyte biology
Tacrolimus
3. Good health
[SDV] Life Sciences [q-bio]
surgical procedures
operative
medicine.anatomical_structure
Cytokine
cytokines/cytokine receptors
Immunology
animal models: nonhuman primate
business
Papio
Zdroj: American Journal of Transplantation
American Journal of Transplantation, 2019, ⟨10.1111/ajt.15543⟩
American Journal of Transplantation, Wiley, 2019, ⟨10.1111/ajt.15543⟩
ISSN: 1600-6135
1600-6143
Popis: International audience; 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.
Databáze: OpenAIRE
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