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Relevance of cytotoxic alloreactivity under different immunosuppressive regimens in clinical islet cell transplantation

Authors :
P. W. M. van der Meer-Prins
M. F. J. Versteeg-Van der Voort Maarschalk
Robert Hilbrands
Daniel Pipeleers
Bart O. Roep
Bart Keymeulen
Gaby Duinkerken
Pieter Gillard
Chantal Mathieu
V. A. L Huurman
F.H.J. Claas
D.L. Roelen
Source :
Clinical and Experimental Immunology. 156:141-148
Publication Year :
2009
Publisher :
Oxford University Press (OUP), 2009.

Abstract

Summary 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.

Details

ISSN :
13652249 and 00099104
Volume :
156
Database :
OpenAIRE
Journal :
Clinical and Experimental Immunology
Accession number :
edsair.doi.dedup.....fc9d9e6e9373d1d245eb21754fdef03d
Full Text :
https://doi.org/10.1111/j.1365-2249.2008.03812.x