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Heterogeneity in P‐glycoprotein (multidrug resistance) activity among murine peripheral T cells: Correlation with surface phenotype and effector function
Author(s) -
Bommhardt Ursula,
Cerottini JeanCharles,
MacDonald H. Robson
Publication year - 1994
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830241208
Subject(s) - biology , p glycoprotein , efflux , il 2 receptor , rhodamine 123 , t cell , phenotype , microbiology and biotechnology , cytotoxic t cell , immunology , in vitro , biochemistry , immune system , multiple drug resistance , gene , antibiotics
Abstract P‐glycoprotein (P‐gly) is the transmembrane efflux pump responsible for multidrug resistance in tumor cells. Functional P‐gly activity can be conveniently assessed microfluorometrically using the fluorescent dye rhodamine 123 (Rh123), which is an artificial substrate for the P‐gly transporter. Here we assess P‐gly activity in subsets of mouse peripheral T lymphocytes using the Rh123 efflux assay. Our data indicate that virtually all CD8 + cells extrude Rh123 efficiently, whereas only a subset of CD4 + cells exhibit P‐gly activity. Correlation of P‐gly activity in CD4 + cells with the expression of a panel of surface markers revealed that cells bearing an “activated/memory” phenotype (CD45RB − , CD44 hi , CD62L − , CD25 + , CD69 + ) were exclusively found in the fraction that can extrude Rh123. In contrast “naive” phenotype CD4 + cells (CD45RB + , CD44 lo , CD62L + , CD25 − , CD69 − ) could be further subdivided into two major subsets based on P‐gly activity. In functional studies of sorted cell populations the Rh123‐extruding subset of “naive” CD4 + cells proliferated more strongly and secreted higher levels of interleukin (IL)‐2 than its Rh123‐retaining counterpart when activated by a variety of polyclonal stimuli. Furthermore, this subset produced detectable levels of interferon (IFN)‐γ upon stimulation but no IL‐4 or IL‐10. As expected, the Rh123‐retaining “naive” subset produced only IL‐2 after stimulation, whereas the “memory” subset produced IFN‐γ, IL‐4 and IL‐10 in addition to low levels of IL‐2. Collectively, our data indicate that P‐gly activity is a novel parameter that can be used to distinguish a subset of “preactivated” CD4 + cells that would be considered as naive on the basis of their surface phenotype.