Abstract

P741 Aims: The majority of current immunosuppressive protocols for solid organ transplant recipients are based on calcineurin inhibitors, increasingly combined with the anti-proliferative agent mycophenolate mofetil (MMF). We have recently demonstrated that indirect T cell recognition of donor-specific HLA peptides plays an important role in the immunopathogenesis of chronic allograft rejection (CR). We have also previously generated HLA allopeptide specific T cell lines and clones from renal transplant recipients with CR treated with cyclosporine (CsA), azathioprine (Aza) and corticosteroids which were of Th1 phenotype (IFN-γ), while lines and clones from stable patients were of a Th2 (IL-10) phenotype. Methods: For this study we generated T cell lines using peripheral blood lymphocytes (PBLs) from renal transplant recipients treated with MMF plus CsA (n=12) or MMF plus Tac (n=6) with either CR (biopsy, serum creatinine > 2 mg/dl) or stable renal function (SRF, serum creatinine ≤ 2 mg/dl). Results: Generated lines showed a significant response to donor-specific peptide (CR: 24.125 ± 3.256 cpm versus SRF: 4.283 ± 731 cpm). T cell lines from patients with CR produced IFN-γ, but only minimal amounts of IL-10 (548 ± 94 versus 58±12 spots/106 cells) in response to the donor specific peptide. In contrast, T cell lines from patients with SRF produced IL-10 but minimal IFN-γ assessed using ELISPOT (533±37 versus 52±11 spots/106 cells, respectively) and confirmed by ELISA and were CD4 CD25 positive (FACS-analysis). Conclusions: In this study on MMF-based immunosuppression we confirm that CR is associated with a Th1 pattern of cytokine production, while stable renal function is associated with a Th2 phenotype regardless of the immunosuppressive regimen used (CsA or Tac plus MMF versus CsA plus Aza). This analysis may provide an invaluable tool to clarify the potential of current immunosuppressive protocols with MMF enabling the induction of T regulatory cells.

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