Suppression of lymphocyte activation by plasma lipoproteins.
Activation of T-lymphocytes in vitro by the polyclonal mitogen phytohemagglutinin is inhibited by plasma lipoproteins with hydrated densities of less than 1.063 g/ml and which contain the apolipoproteins B (apoB) of hepatic (apoB100) and intestinal (apoB48) origin and apolipoprotein E (apoE). Lipids are not required for suppression of lymphocyte activation. Purified apoE, apoB48, and apoB100 inhibit phytohemagglutinin-induced phospholipid turnover and DNA synthesis. These apolipoproteins share a common role. All are involved with the transport of cholesterol in the aqueous channels of the body, the lymph and blood. However, the absence of a lipid requirement for suppression indicates that the suppressive mechanism is independent of the low-density-lipoprotein receptor pathway, the major pathway through which cells obtain extracellular cholesterol. The suppressive potency of lipoproteins and apolipoproteins in the proliferative phase of polyclonal lymphocyte activation is determined by the ratio of T-lymphocytes to accessory cells (adherent monocytes). Suppression is greatest when the number of monocytes per culture is low and least when the T-cell:adherent cell ratio is about 1:1. Preincubation of lipoproteins directly with adherent cells reduces the ability of the lipoproteins to inhibit lymphocyte proliferation, suggesting that the adherent cels chemically alter the lipoproteins. The physiological importance of the plasma lipoproteins in regulating the immune response of the host will therefore depend on the lymphocyte:monocyte ratio and on the concentration of suppressive lipoproteins in the lymph nodes and spleen.
D001053:Apolipoproteins / Q000097:blood / Q000494:pharmacology; D002791:Cholesterol, Dietary / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000097:blood / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D009000:Monocytes / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D001053:Apolipoproteins; D002791:Cholesterol, Dietary; D008074:Lipoproteins