Intravenous infusion of donor apoptotic leukocytes before transplantation delays allogeneic islet graft rejection through regulatory T cells.

François Mougel; Francis Bonnefoy; Stéphanie Kury-Paulin; Sophie Borot; Sylvain Perruche; Bernadette Kantelip; Alfred Penfornis; Philippe Saas; François Kleinclauss

doi:10.1016/j.diabet.2012.08.008

Intravenous infusion of donor apoptotic leukocytes before transplantation delays allogeneic islet graft rejection through regulatory T cells.

François Mougel ^{1, 2, *} Francis Bonnefoy ² Stéphanie Kury-Paulin ^{1, 2} Sophie Borot ^{1, 2, 3} Sylvain Perruche ² Bernadette Kantelip ⁴ Alfred Penfornis ^{1, 3} Philippe Saas ² François Kleinclauss ^{2, 5}

* Auteur correspondant

1 Service de diabétologie - endocrinologie

2 HOTE GREFFON - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)

3 PCVP / CARDIO - Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920)

4 Laboratoire d'anatomie pathologique [Besancon]

5 Service d'urologie et transplantation rénale

Abstract : AIM: This study describes the ability of intravenous donor apoptotic leukocyte infusion before islet transplantation to delay allogeneic graft rejection and implicates regulatory T cells (T(reg)) in the effect. METHODS: Allogeneic FVB (Friend virus B-type) islet transplants were placed under the kidney capsule of BALB/c recipient mice rendered diabetic by streptozotocin. Apoptotic donor leukocytes were infused intravenously 7 days before transplantation. Foxp3/DTR/GFP transgenic C57BL/6 mice were used as recipients to show depletion of T(reg) after apoptotic cell infusion. Control mice received islet transplants without apoptotic cells. RESULTS: The graft median survival time (MST) in recipient mice was 15±1.5 days when apoptotic cells were infused 7 days prior to transplantation of a 1000-islet-containing allograft and 6±0.5 days in the control mice (P<0.01). The same effect was observed using a 500-islet allograft, with an MST of 9±1.1 days vs. 3±0.8 days with and without (controls) apoptotic cells, respectively (P<0.01). This immunomodulatory effect was not observed when apoptotic cell administration was performed on the day of transplantation. Specific T(reg) depletion in Foxp3/DTR/GFP recipient mice inhibited the beneficial effect of apoptotic cell infusion with an MST of 8±1.5 days after apoptotic cell infusion vs. 2±0.2 days when T(reg) were depleted (P<0.01). Furthermore, T(reg) were specifically detected in the islet grafts of mice infused with apoptotic cells prior to islet transplantation. CONCLUSION: Infusion of donor apoptotic cells 7 days before allogeneic transplantation delays islet allograft rejection through a process involving T(reg).

Type de document :

Article dans une revue

Diabetes and Metabolism, Elsevier Masson, 2012, 38 (6), pp.531-7. 〈10.1016/j.diabet.2012.08.008〉

Domaine :

Sciences du Vivant [q-bio] / Immunologie

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http://www.hal.inserm.fr/inserm-00842358
Contributeur : Philippe Saas <>
Soumis le : lundi 8 juillet 2013 - 14:36:24
Dernière modification le : mercredi 5 septembre 2018 - 17:04:03

Intravenous infusion of donor apoptotic leukocytes before transplantation delays allogeneic islet graft rejection through regulatory T cells.

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Intravenous infusion of donor apoptotic leukocytes before transplantation delays allogeneic islet graft rejection through regulatory T cells.

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