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.
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.
Division of Basic and Clinical Immunology, University of California, Irvine 92717.
S
S
Gupta
C H
CH
Kim
T
T
Tsuruo
S
S
Gollapudi
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D020112:Rhodamine 123; D012235:Rhodamines / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D012235:Rhodamines; D020112:Rhodamine 123