B-cell activation and allosensitization after left ventricular assist device implantation is due to T-cell activation and CD40 ligand expression

Michael Schuster, Alfred Kocher, Ranjit John, Marion Hoffman, Jan Ankersmit, Katherine Lietz, Niloo Edwards, Mehmet Oz, Silviu Itescu

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)211-220
Number of pages10
JournalHuman Immunology
Volume63
Issue number3
DOIs
StatePublished - Jan 1 2002

Keywords

  • Allosensitization
  • CD40L
  • LVAD

Fingerprint

Dive into the research topics of 'B-cell activation and allosensitization after left ventricular assist device implantation is due to T-cell activation and CD40 ligand expression'. Together they form a unique fingerprint.

Cite this