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- Title
Relevance of cytotoxic alloreactivity under different immunosuppressive regimens in clinical islet cell transplantation.
- Authors
Roelen, D. L.; Huurman, V. A. L.; Hilbrands, R.; Gillard, P.; Duinkerken, G.; van der Meer-Prins, P. W. M.; Maarschalk, M. F. J. Versteeg-van der Voort; Mathieu, C.; Keymeulen, B.; Pipeleers, D. G.; Roep, B. O.; Claas, F. H. J.
- Abstract
Islet or β cell transplantation provides a promising cure for type 1 diabetes patients, but insulin-independency decreases frequently over time. Immunosuppressive regimens are implemented attempting to cope with both auto- and alloimmunity after transplantation. We analysed the influence of different immunotherapies on autoreactive and alloreactive T cell patterns and transplant outcome. Patients receiving three different immunosuppressive regimens were analysed. All patients received anti-thymocyte globulin induction therapy. Twenty-one patients received tacrolimus–mycophenolate mofetil maintenance immunosuppression, whereas the other patients received tacrolimus–sirolimus (SIR, n = 5) or SIR only ( n = 5). Cellular autoreactivity and alloreactivity (CTL precursor frequency) were measured ex vivo. Clinical outcome in the first 6 months after transplantation was correlated with immunological parameters. C-peptide levels were significantly different between the three groups studied ( P = 0·01). We confirm that C-peptide production was correlated negatively with pretransplant cellular autoreactivity and low graft size ( P = 0·001, P = 0·007 respectively). Combining all three therapies, cellular autoimmunity after transplantation was not associated with delayed insulin-independence or C-peptide production. In combined tacrolimus–SIR and SIR-treated patients, CTL alloreactivity was associated with less insulin independence and C-peptide production ( P = 0·03). The percentage of donors to whom high CTLp frequencies were measured was lower in insulin-independent recipients ( P = 0·03). In this cohort of islet cell graft recipients, clinical outcome in the first 6 months after transplantation correlates with the applied immunosuppressive regimen. An association exists between insulin-independence and lower incidence of CTL alloreactivity towards donor human leucocyte antigen. This observational study demonstrates the usefulness of monitoring T cell reactivity against islet allografts to correlate immune function with graft survival.
- Subjects
CELL transplantation; PEOPLE with diabetes; IMMUNOTHERAPY; T cells; C-peptide; IMMUNOSUPPRESSION
- Publication
Clinical & Experimental Immunology, 2009, Vol 156, Issue 1, p141
- ISSN
0009-9104
- Publication type
Article
- DOI
10.1111/j.1365-2249.2008.03812.x