Bone marrow cells inhibit the generation of autologous EBV-specific CTL

Yide Jin, Laphalle Fuller, Violet Esquenazi, Bonnie B. Blomberg, Anne Rosen, Andreas G. Tzakis, Camillo Ricordi, Joshua Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Recently, we reported that human bone marrow cells (BMC) inhibited the proliferative (recall) response of lymphocytes to Epstein-Barr virus (EBV) and cytomegalovirus (CMV) protein antigens [12]. To clarify further the effect of BMC on the immune response to viral antigens, we obtained PBL from EBV IgG antibody positive kidney transplant recipients (R) and their living- related donors (LRD) 1 year after renal transplantation and generated EBV- specific CTL in vitro in the presence or absence of autologous BMC. The addition of freshly aspirated autologous iliac crest BMC from either R or LRD caused a significant inhibitory effect on the generation of EBV-specific CTL from CTL precursors, in contrast to the addition of autologous PBL used as controls (62.29 ± 10.85% inhibition using BMC from the kidney transplant recipients; 74.47 ± 15.21% inhibition using BMC from the living-related donors). This inhibitory effect was only exerted during the CTL generation phase; but not in the effector CTL killing phase. The expression of CD94, a component of the killer inhibitory receptor (KIR) on CD3+ cells was elevated in the cultures with BMC, in contrast to the cultures without BMC. The BMC inhibitory effect was partially abrogated by pre-incubation of the CTL effectors with anti-CD94 monoclonal antibody, in contrast with its isotype control. In addition, supernatants obtained from the CTL generating cultures with BMC contained high levels of prostaglandin E2 (PGE2), and EBV-specific CTL activity was inhibited by the addition of exogenous PGE2 in the absence of BMC. The induction of CD40L cell surface expression by anti-CD3 was also decreased on the effector T cell population when BMC were added. There was a concomitant reduction in protein kinase C (PKC) activity. These studies demonstrate that BMC exert an inhibitory effect on T cell-mediated immunity to viral antigens in humans by regulating autologous effector T cell generation and early T cell activation signaling pathways. (C) American Society for Histocompatibility and Immunogenetics, 2000.

Original languageEnglish (US)
Pages (from-to)538-547
Number of pages10
JournalHuman Immunology
Volume61
Issue number6
DOIs
StatePublished - Jun 1 2000

Keywords

  • Bone marrow
  • CTL
  • EBV
  • PGE
  • Transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Bone marrow cells inhibit the generation of autologous EBV-specific CTL'. Together they form a unique fingerprint.

Cite this