Résumé :
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Transplantation of muscle precursor cells (MPC) into dystrophic muscle is a major therapeutic approach in muscular dystrophies. However the clinical benefit of this approach is seriously compromised by the low survival rate of the transplanted cells. One principal reason for the low survival of transplanted MPC is their attack by the host immune response. Immune response in an allogenic transplantation is evoked principally by donor to host incompatibility of the major histocompatibility complex. However, mismatch of minor histocompatibility (mH) contributes to transplant rejection too. At present, the only way to overcome rejection is the continuous administration of non-specific immunosuppressive drugs, a treatment not without serious risk, which do not lead to transplantation tolerance. CD4+CD25+ regulatory T cells (Treg) are a unique subpopulation of CD4 T cells required for the maintenance of peripheral tolerance and with the ability to suppress deleterious immune response in many approaches. Here we demonstrate that immune response to the male mH antigen HY is sufficient to compromised survival of transplanted MPC. Importantly, infusing the host mouse with Treg specific for the male antigen HY, we were able to inhibit both the anti-HY immune response and the rejection process in two models of transplantation in muscle. Moreover, this induced immune tolerance was spread over to other rejection antigens presented in the engrafted cells, opening the way for large choice of therapeutic applications.
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