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

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.

journal_name

Kidney Int

journal_title

Kidney international

authors

Shiu KY,McLaughlin L,Rebollo-Mesa I,Zhao J,Semik V,Cook HT,Roufosse C,Brookes P,Bowers RW,Galliford J,Taube D,Lechler RI,Hernandez-Fuentes MP,Dorling A

doi

10.1038/ki.2015.100

subject

Has Abstract

pub_date

2015-09-01 00:00:00

pages

560-8

issue

3

eissn

0085-2538

issn

1523-1755

pii

S2157-1716(15)32195-X

journal_volume

88

pub_type

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