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

Archive ouverte

Mai, Hoa Le | Nguyen, Thi van Ha | Branchereau, Julien | Poirier, Nicolas | Renaudin, Karine | Mary, Caroline | Belarif, Lyssia | Minault, David | Hervouet, Jérémy | Le Bas-Bernardet, Stéphanie | Soulillou, Jean-Paul | Vanhove, Bernard | Blancho, Gilles | Brouard, Sophie

Edité par CCSD ; Elsevier -

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.

Consulter en ligne

Suggestions

Du même auteur

Caractérisation d’une population de lymphocytes B régulateurs en transplantation rénale

Archive ouverte | Brouard, Sophie | CCSD

International audience. Over the last decade, several populations of B cells with regulatory functions have been identified in an increasing number of pathological conditions. Since for several years we have been in...

IL-7 receptor blockade blunts antigen-specific memory T cell responses and chronic inflammation in primates

Archive ouverte | Belarif, Lyssia | CCSD

International audience. Targeting the expansion of pathogenic memory immune cells is a promising therapeutic strategy to prevent chronic autoimmune attacks. Here we investigate the therapeutic efficacy and mechanism...

IL-7 receptor blockade following T cell depletion promotes long-term allograft survival

Archive ouverte | Mai, Hoa-Le | CCSD

International audience. T cell depletion is commonly used in organ transplantation for immunosuppression; however, a restoration of T cell homeostasis following depletion leads to increased memory T cells, which may...

Chargement des enrichissements...