Achieving Donor-Specific Hyporesponsiveness Is Associated with FOXP3+ Regulatory T Cell Recruitment in Human Renal Allograft Infiltrates

作者: Oriol Bestard , Josep M. Cruzado , Mariona Mestre , Anna Caldés , Jordi Bas

DOI: 10.4049/JIMMUNOL.179.7.4901

关键词:

摘要: Exploring new immunosuppressive strategies inducing donor-specific hyporesponsiveness is an important challenge in transplantation. For this purpose, a careful immune monitoring and graft histology assessment mandatory. Here, we report the results of pilot study conducted twenty renal transplant recipients, analyzing immunomodulatory effects protocol based on induction therapy with rabbit anti-thymocyte globulin low doses, sirolimus, mofetil mycophenolate. Evolution cellular humoral alloimmune response, peripheral blood lymphocyte subsets apoptosis was evaluated. Six-month biopsies were performed to assess histological lesions presence FOXP3 + regulatory T cells (Tregs) interstitial infiltrates. After transplantation, there early transient apoptotic effect, mainly within CD8 HLADR cells, combined sustained enhancement CD4 CD25 +high lymphocytes blood. The incidence acute rejection 35%, all steroid sensitive. Importantly, only pretransplant alloreactivity could discriminate patients at risk develop rejection. Two thirds became hyporesponders 6 24 mo, achievement immunologic state not abrogated by prior episodes. Remarkably, had better function less chronic damage. Donor-specific inhibited depleting which showed donor-Ag specificity. Tregs both infiltrates higher than nonhyporesponders, suggesting that recruitment allograft plays role for acceptance. In conclusion, reaching feasible after transplantation associated Treg graft.

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