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29: B-cell activation and allosensitization after left ventricular assist device implantation is due to T-cell activation and CD40 ligand expression. Schuster M, Kocher A, John R, Hoffman M, Ankersmit J, Lietz K, Edwards N, Oz M, Itescu S; Human immunology 2002 Mar;63(3):211-20. Pubmed Link
Left ventricular assist device (LVAD)
implantation is frequently complicated by B-cell activation and
allosensitization, posing a significant risk to successful transplant
outcome. This study investigated whether B-cell hyperreactivity and
alloantibody production in LVAD recipients involves T-cell dependent
pathways. T-cell calcium flux and nuclear translocation of NFATc were
used to determine states of T-cell activation. Flow cytometry was used
to assess human T- and B-cell activation after culture with LVAD-derived
biomaterial particles. Sera from LVAD recipients and controls were
tested for the presence of anti-HLA antibodies, and for soluble CD40
ligand. LVAD-derived biomaterial induced rapid and sustained calcium
flux into normal T cells, resulting in calcineurin-dependent nuclear
translocation of NFATc. This resulted in increased T-cell expression of
CD40 ligand and subsequent B-cell activation, which was reduced by
inhibitors of T-cell activation (CsA or anti-CD25 mAb) or by anti-CD40
ligand mAb. LVAD recipients demonstrated higher frequencies of anti-HLA
antibodies and serum levels of soluble CD40 ligand compared with heart
failure controls. The results indicate that exposure of human
mononuclear cells to LVAD-derived biomaterial leads to T-cell dependent
B-cell activation via CD40--CD40 ligand interaction, and suggest that
treatment with calcineurin inhibitors or monoclonal antibodies against
either CD25 or CD40 ligand could be effective at preventing B-cell
hyperreactivity and allosensitization after LVAD implantation.
a PDF of
this paper can be provided upon request
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