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 Th1 cells and is constitutively expressed by Th2 cells. Using the inhibitor MK571, we and others also suggested that Mrp1 is necessary for Th cell activation. However, herein, we show that Mrp1-deficient Th cells can be differentiated to a similar extent to Th1 and Th2 cells in vitro and, upon re-stimulation, produce comparable amounts of IL-2, IFNgamma 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 Th1 and Th2 cell differentiation. Intriguingly, MK571 is able to completely block activation of Mrp1-deficient Th cells. Most likely, therefore, the molecule relevant for Th 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 Th1 cells as well as those published in a very recent report in this journal on human Th cells.
Kleemann
Peter
P
Institut fuer Medizinische Mikrobiologie und Krankenhaushygiene, University of Marburg, BMFZ, Hans-Meerweinstrasse, 35043 Marburg, Germany. kleemann@med.uni-marburg.de
Casper
Baerbel
B
Huber
Magdalena
M
Schuetz
John D
JD
Lohoff
Michael
M
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000502:physiology*; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D018927:Anti-Asthmatic Agents; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011422:Propionates; D011804:Quinolines; C059141:verlukast; C421109:multidrug resistance-associated protein 1