PSK and Trx80 inhibit B-cell growth in EBV-infected cord blood mononuclear cells through T cells activated by the monocyte products IL-15 and IL-12

Blood. 2005 Feb 15;105(4):1606-13. doi: 10.1182/blood-2004-06-2406. Epub 2004 Oct 26.

Abstract

Epstein-Barr virus (EBV)-specific immunologic memory is not transferred from mother to child. In vitro infection of cord blood cells can therefore readily lead to the outgrowth of transformed B lymphocytes. We found that the immunomodulator polysaccharide K (PSK) or the mitogenic cytokine truncated thioredoxin (Trx80) inhibited the EBV-induced B-cell proliferation. Using signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) induction as a sign for T- and natural killer (NK) cell activation, we could follow it without any need for cell separation because neither macrophages nor B lymphocytes express SAP. The results suggest the following scenario: EBV infected and activated B lymphocytes. Upon interacting with these cells, T cells became posed for responding to cytokines produced by monocytes. Both PSK and Trx80, which is a secreted C-terminally truncated thioredoxin, activated the monocytes, which then produced cytokines in the presence of the primed T cells. PSK induced interleukin-15 (IL-15), while Trx80 induced IL-12 production. Both cytokines activated the T cells for function. Phosphatidylinositol 3-(PI 3)-kinase and reactive oxygen species (ROSs) were involved in the PSK-induced activation of monocytes. Restimulation of the cultures with EBV-transformed B cells generated specific cytotoxic activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Blocking / pharmacology
  • Antibodies, Monoclonal / pharmacology
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / virology
  • Cells, Cultured
  • Culture Media, Conditioned / analysis
  • Drug Synergism
  • Fetal Blood / cytology*
  • Fetal Blood / immunology
  • Fetal Blood / virology
  • Growth Inhibitors / pharmacology*
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Interleukin-12 / analysis
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / immunology
  • Interleukin-12 / physiology*
  • Interleukin-15 / analysis
  • Interleukin-15 / biosynthesis
  • Interleukin-15 / immunology
  • Interleukin-15 / physiology*
  • K562 Cells
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / virology
  • Lymphocyte Activation / immunology
  • Monocytes / immunology
  • Monocytes / metabolism
  • Peptide Fragments / antagonists & inhibitors
  • Peptide Fragments / pharmacology*
  • Phosphatidylinositol 3-Kinases / physiology
  • Proteoglycans / antagonists & inhibitors
  • Proteoglycans / pharmacology*
  • Reactive Oxygen Species / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes, Cytotoxic / immunology
  • Thioredoxins / antagonists & inhibitors
  • Thioredoxins / pharmacology*

Substances

  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Culture Media, Conditioned
  • Growth Inhibitors
  • Immunosuppressive Agents
  • Interleukin-15
  • Peptide Fragments
  • Proteoglycans
  • Reactive Oxygen Species
  • Trx80 protein, human
  • Interleukin-12
  • polysaccharide-K
  • Thioredoxins
  • Phosphatidylinositol 3-Kinases