The multidrug resistance protein 1: A functionally important activation marker for murine Th1 cells

Previously, we described the expression of an energy-dependent pump in rest ing murine Th2 (but not resting Th1) cells which extruded the fluorescent d ye Fluo-3. After stimulation with Ag and APCs, Th1 cells also expressed thi s pump. Furthermore, expression of the murine multidrug resistance protein I (mrp1) correlated with the presence of the pump. In this study, we report that Fluo-3 is indeed transported by murine mrp1 or its human ortholog MRP 1, as revealed by transfection of HEK 293 cells with mrp1 or MRP1 cDNA, Lik e antigenic activation, IL-2 dose-dependently enhanced the Fluo-3-extruding activity in murine Th1 cells, Although TNF-alpha and IL-12 by themselves o nly weakly enhanced Fluo-3 extrusion, each of them did so in strong synergi sm with IL-2, An Ab directed against mrp1 was used to quantify the expressi on of mrp1 protein in T cells at the single-cell level. Like the Fluo-3 pum p, mrp1 protein expression was enhanced by IL-2, Immunohistochemical studie s using confocal laser microscopy indicated that mrp1. is localized mainly at the plasma membrane. In addition, protein expression of mrp1 was induced in V beta 8(+)CD4(+) T cells 12 h after in vivo application of Staphylococ cal enterotoxin B, Finally, mrp1 was functionally relevant during the activ ation process of Th1 cells, because T cell activation could be suppressed b y exposure of cells to the mrp1 inhibitor MK571. Thus, we present mrp1 as a novel, functionally important activation marker for Th1 cells and short-te rm in vivo activated CD4(+) T cells, whereas its expression seems to be con stitutive in Th2 cells.