title: 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.
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.
authors.affiliation: Microbiology and Tumor Biology Center, Karolinska Institute, Box 280, 171 77 Stockholm, Sweden. anquan.liu@mtc.ki.se
authors.forename: Anquan
authors.initials: A
authors.lastname: Liu
authors.forename: Jack L
authors.initials: JL
authors.lastname: Arbiser
authors.forename: Arne
authors.initials: A
authors.lastname: Holmgren
authors.forename: George
authors.initials: G
authors.lastname: Klein
authors.forename: Eva
authors.initials: E
authors.lastname: Klein
mesh_terms: D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000821:virology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000032:analysis; D004357:Drug Synergism; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology / Q000821:virology; D006131:Growth Inhibitors / Q000494:pharmacology*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D018664:Interleukin-12 / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D019409:Interleukin-15 / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D020014:K562 Cells; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011509:Proteoglycans / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013879:Thioredoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D017077:Culture Media, Conditioned; D006131:Growth Inhibitors; D007166:Immunosuppressive Agents; D019409:Interleukin-15; D010446:Peptide Fragments; D011509:Proteoglycans; D017382:Reactive Oxygen Species; C427943:Trx80 protein, human; D018664:Interleukin-12; C010770:polysaccharide-K; D013879:Thioredoxins; D019869:Phosphatidylinositol 3-Kinases