Myeloid-derived suppressor cells accumulate in kidney allograft tolerance and specifically suppress effector T cell expansion - PubMed (original) (raw)

. 2008 Jun 15;180(12):7898-906.

doi: 10.4049/jimmunol.180.12.7898.

Thomas Haudebourg, Flora Coulon, Michèle Heslan, Fabienne Haspot, Nicolas Poirier, Romain Vuillefroy de Silly, Claire Usal, Helga Smit, Bernard Martinet, Pamela Thebault, Karine Renaudin, Bernard Vanhove

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Myeloid-derived suppressor cells accumulate in kidney allograft tolerance and specifically suppress effector T cell expansion

Anne-Sophie Dugast et al. J Immunol. 2008.

Abstract

The immune tolerance to rat kidney allografts induced by a perioperative treatment with anti-CD28 Abs is associated with a severe unresponsiveness of peripheral blood cells to donor Ags. In this model, we identified an accumulation in the blood of CD3(-)class II(-)CD11b(+)CD80/86(+) plastic-adherent cells that additionally expressed CD172a as well as other myeloid markers. These cells were able to inhibit proliferation, but not activation, of effector T cells and to induce apoptosis in a contact-dependent manner. Their suppressive action was found to be under the control of inducible NO synthase, an enzyme also up-regulated in tolerated allografts. Based on these features, these cells can be defined as myeloid-derived suppressor cells (MDSC). Interestingly, CD4(+)CD25(high)FoxP3(+) regulatory T cells were insensitive in vitro to MDSC-mediated suppression. Although the adoptive transfer of MDSC failed to induce kidney allograft tolerance in recently transplanted recipients, the maintenance of tolerance after administration of anti-CD28 Abs was found to be dependent on the action of inducible NO synthase. These results suggest that increased numbers of MDSC can inhibit alloreactive T cell proliferation in vivo and that these cells may participate in the NO-dependent maintenance phase of tolerance.

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