Multidrug-resistance-associated protein 1 (Mrp1) is probably not required for murine Th cell activation

Previously, we have demonstrated that multidrug-resistance-associated protein 1 (Mrp1) represents an activation marker for murine T(h)1 cells and is constitutively expressed by T(h)2 cells. Using the inhibitor MK571, we and others also suggested that Mrp1 is necessary for T-h cell activation. However, herein, we show that Mrp1-deficient T-h cells can be differentiated to a similar extent to T(h)1 and T(h)2 cells in vitro and, upon re-stimulation, produce comparable amounts of IL-2, IFN gamma and IL-4. Mrp1-deficient mice are equally susceptible than wild-type mice to infection with the protozoan parasite Leishmania major, a well-respected model for in vivo T(h)1 and T(h)2 cell differentiation. Intriguingly, MK571 is able to completely block activation of Mrp1-deficient T-h cells. Most likely, therefore, the molecule relevant for T-h cell activation which is blocked by MK571 is different from Mrp1. While these results are compatible with our previously reported data on Mrp1 expression, they contradict our previous conclusions about Mrp1 function in murine T(h)1 cells as well as those published in a very recent report in this journal on human T-h cells.