Heterogeneity in P-glycoprotein (multidrug resistance) activity among murine peripheral T cells: correlation with surface phenotype and effector function

Détails

ID Serval
serval:BIB_0D57335403EA
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Heterogeneity in P-glycoprotein (multidrug resistance) activity among murine peripheral T cells: correlation with surface phenotype and effector function
Périodique
European Journal of Immunology
Auteur(s)
Bommhardt  U., Cerottini  J. C., MacDonald  H. R.
ISSN
0014-2980 (Print)
Statut éditorial
Publié
Date de publication
12/1994
Volume
24
Numéro
12
Pages
2974-81
Notes
Journal Article --- Old month value: Dec
Résumé
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-, CD44hi, CD62L-, CD25+, CD69+) were exclusively found in the fraction that can extrude Rh123. In contrast "naive" phenotype CD4+ cells (CD45RB+, CD44lo, 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)-gamma 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-gamma, 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.
Mots-clé
Age Factors Animals Antigens, CD45/metabolism Base Sequence CD4-Positive T-Lymphocytes/*metabolism Cytokines/metabolism DNA Primers/chemistry Immunophenotyping Lymphocyte Activation Mice Mice, Inbred BALB C Mice, Inbred C57BL Molecular Sequence Data P-Glycoprotein/*metabolism Rhodamine 123 Rhodamines/metabolism T-Lymphocyte Subsets/*metabolism
Pubmed
Web of science
Création de la notice
28/01/2008 12:13
Dernière modification de la notice
20/08/2019 13:34
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