The regulation by low-density lipoproteins of the activation of oxidative enzyme-primed lymphocytes is governed by transferrin.
The activation of T lymphocytes was regulated in vitro by low-density lipoproteins (LDL). Not all prereplicative events induced by the oxidative enzymatic mitogens neuraminidase and galactose oxidase (NAGO) were susceptible to inhibition by LDL. The accessory cell-independent early blastogenic response was not suppressed. LDL suppressed accessory cell-dependent responses, and the extent of LDL suppression, depended on the concentration of transferrin. A gradient of transferrin determined the point in the cell cycle at which NAGO-primed lymphocytes were suppressed by LDL. When transferrin was low (0-10 micrograms/ml) and in serum-free medium (SFM), LDL suppressed the expression of cell surface receptors for interleukin-2 (IL-2R) and transferrin (TfR), the late blastogenic response prior to DNA replication (72 hr), and DNA replication. At higher levels of transferrin, about 100 micrograms/ml, the LDL-suppressed cells were IL-2R+, TfR+ and responsive to IL-2, but did not enter S phase. LDL suppression could be ablated by IL-2 and by high levels of transferrin (250-1000 micrograms/ml). In RPMI medium containing serum (FBS), the pattern of LDL suppression was different from that in SFM: fully activated IL-2R+, TfR+ lymphocytes were unresponsive to exogenous IL-2, suggesting that they were blocked at the G1/S boundary. This block was also relieved by transferrin (greater than 100 micrograms/ml). The data suggest that the interplay between transferrin and LDL is a critical factor in the NAGO-induced stimulation of T lymphocytes. LDL and transferrin exert negative and positive control of lymphocyte activation, respectively. In SFM, LDL appear to alter transferrin utilization by accessory cells; in RPMI-FBS, by fully activated T lymphocytes.
D000938:Antigen-Presenting Cells / Q000502:physiology; D002478:Cells, Cultured; D004261:DNA Replication; D005692:Galactose Oxidase / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000502:physiology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000502:physiology*; D009439:Neuraminidase / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013997:Time Factors; D014168:Transferrin / Q000502:physiology*
D007376:Interleukin-2; D008077:Lipoproteins, LDL; D010835:Phytohemagglutinins; D014168:Transferrin; D005692:Galactose Oxidase; D009439:Neuraminidase