It has been shown previously that a specific high-density lipoprotein (HDL) receptor exists on human lymphocytes that recognizes apoprotein (apo) A1 as its ligand, and may be responsible for utilization of HDL lipids to respond optimally to mitogenic stimulation when cultured in serum-free medium supplemented with HDL. To clarify further the relationship between various HDL lipids used by lymphocytes and HDL receptor activity, the lipid composition of the cells and the regulation of HDL and low-density lipoprotein (LDL) receptors on freshly isolated lymphocytes and mitogen-activated T-blasts after treatment with lipoproteins, liposomes or fatty acids were investigated. Our data show that the linear increase in cell proliferation correlates with the presence of HDL in fatty-acid-free culture medium in the concentration range of HDL receptor saturation. Decreased binding/uptake of dioctadecylindocarbocyanine (DiI)-fluorescence-labelled HDL by freshly isolated lymphocytes was observed in the presence of unlabelled HDL in 4-day culture, whereas T-blast binding/uptake was down-regulated by preincubation not only with HDL but also with LDL. T-blasts pretreated with HDL showed increased cellular contents of phosphatidylcholine, oleic acid (C18:1,n-9) and linoleic acid (C18:2,n-6), which are essential for optimal proliferation of mitogen-stimulated lymphocytes. Furthermore, DiI-HDL binding on lymphocytes was down-regulated by up to 20% (resting T cells) and 50% (T-blasts) when cultured in the presence of apoA1-phosphatidylcholine liposomes (T-blasts only), oleic acid or linoleic acid, but not by stearic acid (C18:0). The results indicate that HDL provide lymphocytes with essential fatty acids, which in turn regulate HDL receptor activity.

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