Lymphocyte Transformation Activity Research Articles

Lymphocyte transforming activity in the serum of patients with hepatic disease.

Abstract. The stimulating effect of serum of patients with hepatic disease on normal peripheral blood lymphocytes cultured in vitro was studied. In 25 out of 27 patients serum stimulated lymphocyte transformation as determined morphologically and by increased uptake of 3H‐thymidine and 3H‐cytidine. Rapidly increasing RNA synthesis was found during the first 24 h of incubation. DNA synthesis was found to be at its maximum between days 3 and 4. The behaviour of the serum of patients found to be positive for Australia antigen and patients with other hepatic disease was comparable. It was demonstrated that the factor in serum which initiates lymphocyte transformation, is in the globulin fraction.

“Nonspecific” Stimulation of Lymphocyte Transformation by Cellular Fractions and Acid Extracts of Group a Streptococci

Abstract Hot hydrochloric acid extracts of group A streptococcal cells of types 5, 12 and 19 induced “nonspecific” blast-transformation and increased thymidine-14C incorporation by adult and cord blood lymphocytes of normal human donors. A similar degree of transformation was induced by preparations of streptococcal cell walls and cell membranes and by hot acid extracts of these cell components. Streptococcal cytoplasm was found to contain an inhibitor of phytohemagglutinin-induced transformation and of spontaneous transformation of cord blood lymphocytes. Treatment of streptococcal cytoplasm with hot hydrochloric acid resulted in the appearance or release of lymphocyte transforming activity in such preparations. The lymphocyte transforming activity of streptococcal acid extracts was unaffected by digestion with ribonuclease, trypsin, chymotrypsin, and pepsin. After gel filtration on Sephadex G-75, acid extracts of streptococcal cell membranes, cell walls and cytoplasm all exhibited their major transforming activity in a peak with maximum at Kd 0.36, suggesting a similar average molecular size for the transforming agent or agents derived from these components. The “nonspecific” mitogenic activity of acid extracts of streptococcal cells resembled that of streptolysin S preparations with respect to enzyme susceptibility and dose-response. Hot acid-treated streptolysin S preparations retained most of their transforming activity, while their hemolytic activity was completely destroyed. These data raise the possibility that the transforming activities of streptococcal cell acid extracts and of streptolysin S preparations are attributable to a similar or identical constituent.

Lymphocyte Transforming Activity in the Serum of Patients with Hepatic Disease

Lymphocyte Transforming Activity in the Serum of Patients with Hepatic Disease

Dissociation of hemolytic and lymphocyte-transforming activities of streptolysin S preparations.

The ability of streptolysin S preparations to induce high percentages of transformation in human peripheral blood lymphocytes was confirmed in a series of apparently healthy donors. Transforming activity was not demonstrated in the two media used for streptolysin S production, nor in control preparations in which a strain each of Streptococcus viridans, Staphylococcus aureus (nonhemolytic), and Diplococcus pneumoniae was substituted for the beta hemolytic streptococcal strain used for streptolysin S production. The relation of the hemolytic activity to the lymphocyte transforming activity of streptolysin S preparations was studied by means of inactivation and fractionation experiments. Heating produced a loss in both activities, but more in the hemolytic than in the transforming activity. The transformation obtained with a heated preparation had a high degree of correlation with that obtained with the unheated preparation in a series of normal subjects and patients with various rheumatic diseases, whose lymphocytes were often less responsive to stimulation with streptolysin S preparations (both heated and unheated) than the lymphocytes of the normal subjects studied. Treatment of streptolysin S preparations with chymotrypsin, vegetable lecithin, or trypan blue (the latter in minute amounts) resulted in preparations with no detectable hemolytic activity but with undiminished lymphocyte transforming activity. Chromatographic fractionations on DEAE-Sephadex columns yielded fractions endowed with transforming but not with hemolytic activity, and other fractions endowed with hemolytic but not with transforming activity. The recovery of the hemolytic activity was not complete and quantitation of the recovery of the transforming activity was not attempted. These experiments indicate that the hemolytic and transforming activities of streptolysin S preparations are independent of each other, and specifically that they are the attributes of two different streptococcal products, one of which is streptolysin S. The other is a nonhemolytic streptococcal product present in streptolysin S preparations but previously unrecognized. Some implications of these findings are discussed.