Immunoregulation by low density lipoproteins in man: low density lipoprotein inhibits mitogen-stimulated human...

Low density lipoprotein (LDL, d 1.020-1.050 g/ml), isolated from normal human plasma by ultracentrifugation, inhibited mitogen-stimulated proliferation of human lymphocytes in a concentration-dependent manner. In order to characterize the inhibition more fully, the effect of LDL on initial lymphocyte activation and subsequent DNA synthesis was investigated. LDL had no effect on lymphocyte blast transformation assessed by quantitating the change in volume of the stimulated cells after a 24-hour incubation. Moreover, initial lymphocyte activation assessed by mitogen-stimulated RNA or protein synthesis was not inhibited by LDL. Finally, the acquisition of transferrin or T cell growth factor receptors by the activated lymphocytes was not affected by LDL. DNA synthesis, evaluated by measuring the incorporation of [3H]thymidine between 30 and 48 hours of culture was inhibited by LDL in a concentration-dependent manner. The DNA content of individual mitogen-stimulated cells was analyzed by flow cytometry after mithramycin staining. These studies confirmed that LDL inhibited DNA synthesis in the initially activated lymphocytes. In addition, LDL in concentrations that did not inhibit initial DNA synthesis did suppress cell division and lymphocyte proliferation. These results indicate that LDL inhibits lymphocyte responses by exerting inhibitory effects on DNA synthesis, cell division, and subsequent growth of the activated cells rather than by altering initial lymphocyte blast transformation. LDL thus may play a role in regulating clonal expansion of activated lymphocytes during immune responses.