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Sabbah S;Liew A;Brooks AM;Kundu R;Reading JL;Flatt A;Counter C;Choudhary P;Forbes S;Rosenthal MJ;Rutter MK;Cairns S;Johnson P;Casey J;Peakman M;Shaw JA;Tree TIM;
American Journal Of Transplantation
Autoreactive T-cell profiles are altered following allogeneic islet transplantation with alemtuzumab induction and re-emerging phenotype is associated with graft function.
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Islet transplantation is an effective therapy for life-threatening hypoglycemia, but graft function gradually declines over time in many recipients. We characterized islet-specific T-cells in recipients within an islet transplant program favoring alemtuzumab lymphodepleting induction and examined associations with graft function. 58 recipients were studied: 23 pre-transplant; 40 post-transplant (including 5 with pre-transplant phenotyping). The proportion with islet-specific T-cell responses was not significantly different over time (pre-Tx: 59%; 1-6m post-transplant: 38%; 7-12m: 44%; 13-24m: 47%; >24m: 45%). However, phenotype shifted significantly, with IFN--dominated response pre-transplant replaced by IL-10-dominated response in the 1-6m post-transplant group, reverting to predominantly IFN--oriented response in the >24m group. Clustering analysis of post-transplant responses revealed two main agglomerations, characterized by IFN- and IL-10 phenotype respectively. IL10-oriented post-transplant response was associated with relatively low graft function. Recipients within the IL-10+ cluster had a significant decline in C-peptide levels in the period preceding the IL-10 response, but stable graft function following the response. In contrast, an IFN- response was associated with subsequently decreased C-peptide. Islet transplantation favoring alemtuzumab induction is associated with an initial altered islet-specific T-cell phenotype but reversion towards pre-transplant profiles over time. Post-transplant autoreactive T-cell phenotype may be a predictor of subsequent graft function.
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