All authors are from JDRF Center for Beta Cell Therapy in Diabetes.
Relevance of cytotoxic alloreactivity under different immunosuppressive regimens in clinical islet cell transplantation
Version of Record online: 21 JAN 2009
© 2009 British Society for Immunology
Clinical & Experimental Immunology
Volume 156, Issue 1, pages 141–148, April 2009
How to Cite
Roelen, D. L., Huurman, V. A. L., Hilbrands, R., Gillard, P., Duinkerken, G., Van Der Meer-Prins, P. W. M., Versteeg-van der Voort Maarschalk, M. F. J., Mathieu, C., Keymeulen, B., Pipeleers, D. G., Roep, B. O. and Claas, F. H. J. (2009), Relevance of cytotoxic alloreactivity under different immunosuppressive regimens in clinical islet cell transplantation. Clinical & Experimental Immunology, 156: 141–148. doi: 10.1111/j.1365-2249.2008.03812.x
- Issue online: 11 MAR 2009
- Version of Record online: 21 JAN 2009
- Accepted for publication 7 October 2008
- β cell transplantation;
- cytotoxic T cell;
- islets of Langerhans;
- type 1 diabetes
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.