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Relevance of cytotoxic alloreactivity under different immunosuppressive regimens in clinical islet cell transplantation
- 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.
- Subjects :
- Adult
Cytotoxicity, Immunologic
Graft Rejection
Male
medicine.medical_treatment
T cell
Immunology
Islets of Langerhans Transplantation
Autoimmunity
Lymphocyte Activation
Tacrolimus
Islets of Langerhans
medicine
Humans
Insulin
Immunology and Allergy
Cells, Cultured
Kidney transplantation
Postoperative Care
Sirolimus
Islet cell transplantation
geography
geography.geographical_feature_category
C-Peptide
business.industry
Graft Survival
Alloimmunity
Immunosuppression
Middle Aged
Mycophenolic Acid
medicine.disease
Islet
Transplantation
CTL
Diabetes Mellitus, Type 1
Treatment Outcome
surgical procedures, operative
medicine.anatomical_structure
Translation Studies
Drug Therapy, Combination
Female
business
Immunosuppressive Agents
Follow-Up Studies
T-Lymphocytes, Cytotoxic
Subjects
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