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

Research output: Contribution to journalArticle

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

Fingerprint

Human Herpesvirus 4
Bone Marrow Cells
Living Donors
T-Lymphocytes
Viral Antigens
Dinoprostone
KIR Receptors
Kidney
Cohort Effect
Immunogenetics
CD40 Ligand
Histocompatibility
Cytomegalovirus
Cellular Immunity
Kidney Transplantation
Protein Kinase C
Immunoglobulin G
Monoclonal Antibodies
Lymphocytes
Transplants

Keywords

  • Bone marrow
  • CTL
  • EBV
  • PGE
  • Transplantation

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Jin, Y., Fuller, L., Esquenazi, V., Blomberg, B. B., Rosen, A., Tzakis, A. G., ... Miller, J. (2000). Bone marrow cells inhibit the generation of autologous EBV-specific CTL. Human Immunology, 61(6), 538-547. https://doi.org/10.1016/S0198-8859(00)00120-8

Bone marrow cells inhibit the generation of autologous EBV-specific CTL. / Jin, Yide; Fuller, Laphalle; Esquenazi, Violet; Blomberg, Bonnie B; Rosen, Anne; Tzakis, Andreas G.; Ricordi, Camillo; Miller, Joshua.

In: Human Immunology, Vol. 61, No. 6, 01.06.2000, p. 538-547.

Research output: Contribution to journalArticle

Jin, Y, Fuller, L, Esquenazi, V, Blomberg, BB, Rosen, A, Tzakis, AG, Ricordi, C & Miller, J 2000, 'Bone marrow cells inhibit the generation of autologous EBV-specific CTL', Human Immunology, vol. 61, no. 6, pp. 538-547. https://doi.org/10.1016/S0198-8859(00)00120-8
Jin, Yide ; Fuller, Laphalle ; Esquenazi, Violet ; Blomberg, Bonnie B ; Rosen, Anne ; Tzakis, Andreas G. ; Ricordi, Camillo ; Miller, Joshua. / Bone marrow cells inhibit the generation of autologous EBV-specific CTL. In: Human Immunology. 2000 ; Vol. 61, No. 6. pp. 538-547.
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