Inhibition of DNA synthesis in lymphocytes by dialyzable components of human leukocyte extracts

Regulation of Lymphocyte Transformation by Components Identified in Ultrafiltrates Prepared from Leukocyte Extracts

“…We have previously shown that an ultra filtrate of DLE contains substances which are able to augment blastogenic responses of lymphocytes, and that three inhibitory components can be partially pu rified by gel filtration on Sephadex G-10 [8,9]. In this report, we show that the augmentor present in the ul trafiltrate is able to enhance the blastogenic response of lymphocytes to mitogen (especially PH A), and that it selectively stimulates T cells but not B cells.…”

“…It has also been reported that DLE contains com ponents which augment antigen-and mitogen-in duced lymphocyte transformation [3][4][5][6][7], and we have also shown that the enhancing effect on lymphocyte transformation in unstimulated culture is present in B-G-2 fraction of S* fraction (antigen-independent effect) [8,9]. In the present paper, the enhancing effect of the S* fraction (MW < 5,000) was shown to be resi dent in the S*S fraction (MW < 1,000), and to be very marked in PPD-stimulated cultures (antigen-depend ent effect).…”

“…1-3 appeared to correspond to thymidine itself as noted in a separate study [8]. Although DLE has frequently been reported to be toxic to lympho cytes in culture [26], the effect of these inhibitory com ponents on lymphocyte transformation do not appear to be due to a cytotoxic effect because the cell viability in these studies was greater than 90% in all cases, and these effects were reversible by cell washing.…”

“…The aug menter is recoverable in association with the major fluram peak (G-2 to G-3 fraction) by gel filtration of the S* fraction (MW < 5,000) on a Sephadex G-10 col umn. As a result of in vitro experiments, we have re ported that the S* fraction of leukocyte extracts con tain materials which increase and decrease the 3H-thymidine uptake of peripheral lymphocytes in un stimulated cultures (8,9], In this study, we demon strated that these effects of the S* fraction (MW <5,000) were almost exclusively resident in the S*S fraction (M W < 1,000). The suppressive effects of DLE on lymphocyte transformation have been esta blished to be nicotinamide [16] and thymidine [8].…”

“…As a result of in vitro experiments, we have re ported that the S* fraction of leukocyte extracts con tain materials which increase and decrease the 3H-thymidine uptake of peripheral lymphocytes in un stimulated cultures (8,9], In this study, we demon strated that these effects of the S* fraction (MW <5,000) were almost exclusively resident in the S*S fraction (M W < 1,000). The suppressive effects of DLE on lymphocyte transformation have been esta blished to be nicotinamide [16] and thymidine [8]. In the present study, ultrafiltered leukocyte extracts were shown to contain histamine and prostaglandins (G-2 to G-3 fraction), and decreased the 3H-thymidine up take of peripheral lymphocytes in unstimulated cul tures.…”