TGF-b1 and donor dendritic cells are common key components in donor-specific blood transfusion and anti-class II heart graft enhancement, whereas tolerance induction also required inflammatory cytokines down-regulation - Archive ouverte HAL Access content directly
Journal Articles European Journal of Immunology Year : 2001

TGF-b1 and donor dendritic cells are common key components in donor-specific blood transfusion and anti-class II heart graft enhancement, whereas tolerance induction also required inflammatory cytokines down-regulation

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Abstract

Heart allograft tolerance in adult recipients can be induced in the LEW.1W to LEW.1A congeneic strain combination by pre-graft donor-specific blood transfusion (DST). Long-term survivors accept LEW.1W graft but reject third party skin grafts. As tolerant recipients of heart allografts showed an increase in anti-donor class II antibodies, we hypothesize that these antibodies could be instrumental in tolerance induction. However, anti-donor MHC class II alone prolonged graft survival but did not induce heart allograft tolerance in this combination. We analyzed the immune response patterns in heart allograft recipients following the injection of anti-donor class II antibodies (prolongation) or DST priming (tolerance). As suggested by the different phenomena, several immunological patterns were strikingly different between the two models. In strong contrast to DST-tolerant recipients, at 5 days after transplantation, neither Th1/Th2 nor inflammatory cytokines were inhibited in recipients treated with anti-donor class II antibodies, in which only prolongation of graft survival was induced. Nevertheless, in both models, depletion of resident dendritic cells (DC) from donor hearts inhibited tolerance induction (DST) or shortened allograft survival (anti-donor class II antibodies). Moreover, TGF-g 1 was not down-regulated and administration of neutralizing anti-TGF-g 1 antibody, which inhibited tolerance induction (DST), also shortened allograft survival (anti-donor class II antibodies). These results suggest that, in these two MHC class II-restricted models, both TGF-g 1 and donor DC have a pivotal role in prolonging graft survival. However, in the days following transplantation, further inhibition of inflammatory cytokine production, particularly Th1 and macrophage-derived cytokines is required for tolerance induction.
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inserm-03349726 , version 1 (20-09-2021)

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Katia Gagne, Sophie Brouard, Marina Guillet, Maria-Cristina Cuturi, Jean-Paul Souilillou. TGF-b1 and donor dendritic cells are common key components in donor-specific blood transfusion and anti-class II heart graft enhancement, whereas tolerance induction also required inflammatory cytokines down-regulation. European Journal of Immunology, 2001, 31 (10), pp.3111-20. ⟨10.1002/1521-4141(2001010)31:10<3111::aid-immu3111>3.0.co;2-6⟩. ⟨inserm-03349726⟩
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