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B-lymphocytes support and regulate indirect T-cell alloreactivity in individual patients with chronic antibody-mediated rejection

Research output: Contribution to journalArticle

Kin Y Shiu, Laura Mclaughlin, Irene Rebollo-mesa, Jingyue Zhao, Vikki Semik, H Terence Cook, Candice Roufosse, Paul Brookes, Robert W Bowers, Jack Galliford, David Taube, Robert I Lechler, Maria P Hernandez-fuentes, Anthony Dorling

Original languageEnglish
Pages (from-to)560-568
Number of pages9
JournalKidney International
Early online date1 Apr 2015
DOIs
Publication statusPublished - 1 Sep 2015

King's Authors

Abstract

We explored how B-lymphocytes influence in vitro T-cell alloresponses in patients with antibody-mediated rejection (AMR), testing whether B-cells would be preferentially involved in this group of patients. Peripheral blood mononuclear cells were collected from 65 patients having biopsy: 14 patients with AMR and 5 with no pathology on protocol; 38 with AMR and 8 with nonimmunologic damage on ‘for cause’. Using enzyme-linked immunosorbent spot assays, we found interferon-γ production by indirect allorecognition in 45 of 119 total samples from the 65 patients. B-cells preferentially processed and presented donor alloantigens in samples from AMR patients. In a further 25 samples, B-cell–dependent allo-specific reactivity was shown by depletion of CD25+ cells and these individuals had higher percentages of CD4CD25hi cells. In 21 samples, reactivity was shown by depletion of CD19+ cells, associated with polarized cytokine production toward IL-10 after polyclonal activation by IgG/IgM. Overall, this shows a significant contribution by B-cells to indirect donor-specific T-cell reactivity in vitro in patients with AMR. Active suppression by distinct phenotypes of T- or B-cells in approximately half of the patients indicates that chronic AMR is not characterized by a universal loss of immune regulation. Thus, stratified approaches that accommodate the heterogeneity of cell-mediated immunity might be beneficial to treat graft dysfunction.

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