A8.32 Regulatory B-cell supress T-cell proliferation through a TGFβ/IDO axis and are deficient in chronic humoral rejection.

Abstract : In kidney transplantation, B cell is increasingly identified as an important determinant for graft outcome. Chronic antibody mediated rejection (cABMR) represent today the major complication in clinic. Patients with cABMR display a unique B cell phenotype characterised by a disturbance in B cell distribution. Here, the aim of our study was to research if cABMR B cells present also impaired regulatories functions. Experiments are realised in 12 stable patients (ST) (delay from graft >12 months, no rejection, proteinuria <0.5g/24h, PRA <10%, no DSA and a one year biopsy without allograft glomerulopathy or rejection), 14 patients with cABMR (positive DSA, allograft glomerulopathy and/or C4d staining) and 17 controls (blood donors). B-cell functions were analysed using coculture with B and T cells. Proliferation and Th1 cytokine secretion of isolated CFSE labelled T cells in presence of autologous B cells was compared between the 3 groups. T cells were stimulated with anti CD3 and anti CD28, and co-cultured with CpG-activated B cells. Suppressive cytokines like TGFβ and IL-10 and the regulatory enzyme indoleamine 2,3-dioxygenase (IDO) were evaluated during the course of the culture. First, we have demonstrated that compared with situation of stable graft function and healthy volunteers, B cells from cABMR patients display an impaired regulatory function on T cell proliferation and Th1 production. Furthermore, B cells induce more T regulatory cells (Tregs) in coculture after 4 days in HV and ST groups compared to cABMR group (p<10(-3)). We also evidenced that TGFβ and IDO expressed by B cells are involved in inhibition of T cell proliferation and Treg cells generation in HV and ST patients. We additionally shown that B cells from cABMR patients present a failure of TGFβ and IL-10 secretion in co-culture associated with a significantly decrease of IDO production leading to a defect in the capacity of activated-B cells to induce Treg cells and control T cell responses. Finally, B cells from cABMR patients display functional abnormalities as evidenced by the loss of B cell suppressive activity. This work represents interesting perspectives with the discovered of new cellular targets who can be might guide therapy in transplantation in the future.
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Annals of the Rheumatic Diseases, BMJ Publishing Group, 2014, 73 Suppl 1, pp.A89. 〈10.1136/annrheumdis-2013-205124.206〉
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http://hal.univ-brest.fr/hal-00950055
Contributeur : Geneviève Michel <>
Soumis le : jeudi 20 février 2014 - 16:10:57
Dernière modification le : lundi 18 décembre 2017 - 14:40:13

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A. Nouel, I. Segalen, C. Jamin, J.-O. Pers, Yves Le Meur, et al.. A8.32 Regulatory B-cell supress T-cell proliferation through a TGFβ/IDO axis and are deficient in chronic humoral rejection.. Annals of the Rheumatic Diseases, BMJ Publishing Group, 2014, 73 Suppl 1, pp.A89. 〈10.1136/annrheumdis-2013-205124.206〉. 〈hal-00950055〉

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