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. 2016 Mar 1;7:73. doi: 10.3389/fimmu.2016.00073

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Copyright © 2016 Gabriel, Bon, Chen, Wekerle, Bushell, Fehr and Cippà.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Tolerance induction by ABT-737 requires Tregs. (A) Experimental setup of mixed chimerism tolerance protocol: B6 recipients were treated with five injections of ABT-737 and CsA during the 3 days prior transplantation of CBA bone marrow cells on day 0. Anti-CD154 antibodies were administered 6 h before bone marrow transplantation, and ABT-737/CsA treatment was continued until day 11 after transplantation. Tregs were blocked by anti-GITR antibodies (circles) or depleted by anti-CD25 antibody administration (squares) at day −1. Eight weeks after transplantation, mice received CBA donor-type (black) and BALB/c third party (white) skin grafts and survival of grafts was monitored until rejection. (B) Graft survival of control group and (C) of Treg blocked/depleted groups, n = 7/group. (D) Representative FACS plots of peripheral CD4⁺ cell chimerism in control mouse and Treg depleted mouse 2 months after bone marrow transplantation. Tolerance protocol shown in (B) was repeated several times and Treg blockade/depletion by anti-GITR and anti-CD25 once each.