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J Clin Immunol. 1992 Nov;12(6):451-8.

Preferential expression and activity of multidrug resistance gene 1 product (P-glycoprotein), a functionally active efflux pump, in human CD8+ T cells: a role in cytotoxic effector function.

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1
Division of Basic and Clinical Immunology, University of California, Irvine 92717.

Abstract

The multidrug resistance gene 1 (mdr 1) product, the P-glycoprotein (Pgp), is a 170-kD transmembrane transport protein, whose overexpression is associated with multidrug resistance in cancer cells and in chloroquine-resistant Plasmodium falciparum infection. In this study we show that normal freshly isolated human lymphocytes express low levels of mdr 1 mRNA and membrane Pgp. Although Pgp is expressed in both CD4+ and CD8+ T cells, it is preferentially expressed in CD8+ T cells. Activation of T lymphocytes with phytohemagglutinin leads to an amplification of both mdr 1 mRNA and membrane Pgp in T cells. P-glycoprotein in T cells is a functionally active efflux pump as demonstrated by decreased retention of rhodamine-123 and its increased accumulation by cyclosporin A, an inhibitor of Pgp function. In addition, MRK-16 antibody increased accumulation of Rh123 in CD8+ T cells. Furthermore, MRK16 anti-P-glycoprotein monoclonal antibody, in a concentration-dependent manner, inhibited T lymphocyte-mediated cytotoxicity. These data suggest a physiologic role of P-glycoprotein in cytotoxic T-lymphocyte effector function.

PMID:
1363104
[Indexed for MEDLINE]

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