![]() Induction and maintenance of donor-specific allo-immune tolerance is dependent on the balance of effector T cells and regulatory CD4 + T cells (T reg cells) 1. Therefore pDCs can be an attractive immunotherapeutic target in addition to plerixafor treatment. Our pharmacological approach allowed to increase T reg cell numbers due to pDC-mediated immune regulation. ![]() Furthermore, in vivo pDC-depletion abrogated the plerixafor-mediated T reg cell number increase and reduced allograft survival. Noteworthy, this was accompanied by a plerixafor-dependent plasmacytoid dendritic cells-(pDCs)-mobilization. Although less CD3 + T cell infiltrated, higher T reg cell numbers were observed. Moreover, fibrosis and myocyte lesions were reduced. Thus, we performed fully-mismatched heart transplantations and found combination treatment to result in prolonged allograft survival. We hypothesized a synergism of the immunotolerogenic effects of rapamycin (mTOR inhibition) and plerixafor (CXCR4 antagonist) for T reg cell induction. Thus, there is an unmet need for the direct induction of graft-specific T reg cells. ![]() Although adoptive T reg cell transfer has been proposed, major challenges include graft-specificity and stability. Allograft-specific regulatory T cells (T reg cells) are crucial for long-term graft acceptance after transplantation.
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