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Secretory Phospholipase A2-IID Is an Effector Molecule of CD4⁺ CD25⁺ Regulatory T Cells
Caroline E. von Allmen, Nicole Schmitz, Monika Bauer, Heather J. Hinton, Michael O. Kurrer, Regula B. Buser, Myriam Gwerder, Simone Muntwiler, Tim Sparwasser, Roger R. Beerli, Martin F. Bachmann and Dan R. Littman
Proceedings of the National Academy of Sciences of the United States of America
Vol. 106, No. 28 (Jul. 14, 2009), pp. 11673-11678
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/40484009
Page Count: 6
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Suppression by natural CD4⁺ CD25⁺ regulatory T cells (Tregs) is one mechanism by which tolerance is maintained. However, the way in which Tregs mediate suppression is not well understood. Here, we show that secreted phospholipase A2 (sPLA2)-IID is selectively produced by Tregs. sPLA2-IID is a potent mediator of Treg function, because it strongly suppressed proliferation of CD4⁺ and CD8⁺ T cells in vitro and in vivo in a manner independent of its catalytic activity. Furthermore, sPLA2-IID promoted the differentiation of Tregs, presumably via attenuating signaling through the PI3K/Akt/mammalian target of rapamycin pathway. Importantly, administration of a sPLA2-IID-Fc fusion protein inhibited disease development in murine models of colitis and multiple sclerosis, suggesting that sPLA2-IID's immunosuppressive function might be exploited therapeutically.
Proceedings of the National Academy of Sciences of the United States of America © 2009 National Academy of Sciences