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Plasma membrane cholesterol regulates human lymphocyte cytotoxic function

M P Dabrowski, W E Peel, A E Thomson

    European Journal of Immunology
    |November 1, 1980
    PubMed
    Summary
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    Cell membrane cholesterol levels in human lymphocytes are crucial for their function. Adjusting cholesterol content with liposomes or inhibitors significantly impacts lymphocyte cytotoxicity against target cells.

    Area of Science:

    • Immunology
    • Cell Biology
    • Biochemistry

    Background:

    • Cell cholesterol is primarily localized to the plasma membrane.
    • The role of plasma membrane cholesterol in lymphocyte effector functions is not fully understood.

    Purpose of the Study:

    • To investigate the impact of altered cellular cholesterol levels on human lymphocyte cytotoxic functions.
    • To determine if plasma membrane cholesterol content is essential and regulatory for lymphocyte cytotoxicity.

    Main Methods:

    • Human peripheral blood lymphocytes were treated with cholesterol-free and cholesterol-containing liposomes to manipulate cellular cholesterol levels.
    • Cholesterol content was chemically analyzed.
    • Lymphocyte effector functions, including spontaneous, phytohemagglutinin (PHA)-dependent, and antibody-dependent cytotoxicity, were measured.

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  • The effect of 25-hydroxycholesterol, an inhibitor of cholesterol biosynthesis, was also assessed.

    • Main Results:

    • Cholesterol depletion using liposomes inhibited spontaneous and PHA-dependent lymphocyte cytotoxicity.
    • Cholesterol enrichment significantly increased PHA-dependent and antibody-dependent cytotoxicities.
    • Treatment with 25-hydroxycholesterol mimicked the suppressive effects of cholesterol depletion.

    Conclusions:

    • Plasma membrane cholesterol content is essential for human lymphocyte cytotoxic function.
    • Cholesterol levels within lymphocytes play a regulatory role in their ability to perform cytotoxic activities.