Inhibition of the mitogenic response of normal peripheral lymphocytes by extracts or supernatant fluids of a Herpesvirus saimiri lymphoid tumor cell line

Abstract

A Herpesvirus saimiri-infected marmoset lymphoid cell line (MLC-1) was examined for the presence of soluble factors which might affect lymphocyte functions and, therefore, relate to the pathogenesis of lymphoma in vivo. MLC-1 cells, cell extracts, and culture fluids were shown to reduce the spontaneous deoxyribonucleic acid (DNA) synthesis of normal peripheral blood lymphocytes and to completely inhibit their response to phytohemagglutinin (PHA). Suppression of PHA response was demonstrated against a variety of human and nonhuman primate species, with 90 to 95% inhibition occurring at dilutions of extract as great as 1:5,120. Inhibition of this type was also demonstrated using extracts of two of five other lymphoblastoid cell lines tested. Physical-chemical characteristics of the active factor(s) revealed a non-sedimentable, non-dialyzable, trypsin-resistant molecule, which was stable at 56 C for 30 min but inactivated at 80 C for 30 min. The factor(s) also exerted an effect on some but not all established lymphoblastoid cell lines, where DNA, ribonucleic acid, and protein synthesis were all inhibited, with DNA synthesis being the most affected (95% suppression). Cellular respiration was not affected by the presence of the factor(s), and the inhibition of DNA synthesis was reversible after 24 h. Purified human interferon did not reduce the PHA response of normal owl monkey peripheral blood lymphocytes and was less effective against an established lymphoblastoid cell line than the MLC-1 extract. Antiviral activity was also demonstrated in the preparations and may represent interferon, which these cells are known to produce at low levels.