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 Blood, 15 February 2005, Vol. 105, No. 4, pp. 1606-1613.
Prepublished online as a Blood First Edition Paper on October 26, 2004; DOI 10.1182/blood-2004-06-2406.

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IMMUNOBIOLOGY

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

Anquan Liu, Jack L. Arbiser, Arne Holmgren, George Klein, and Eva Klein

From the Microbiology and Tumor Biology Center, Medical Nobel Institute for Biochemistry, Department of Biophysics and Biochemistry, Karolinska Institute, Stockholm, Sweden; and the Department of Dermatology, Emory University School of Medicine, Atlanta, GA.

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.


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A. Liu, H.-E. Claesson, Y. Mahshid, G. Klein, and E. Klein
Leukotriene B4 activates T cells that inhibit B-cell proliferation in EBV-infected cord blood-derived mononuclear cell cultures
Blood, March 1, 2008; 111(5): 2693 - 2703.
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