| Autor: |
De Wilde V; Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium., Van Rompaey N, Hill M, Lebrun JF, Lemaître P, Lhommé F, Kubjak C, Vokaer B, Oldenhove G, Charbonnier LM, Cuturi MC, Goldman M, Le Moine A |
| Jazyk: |
angličtina |
| Zdroj: |
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2009 Sep; Vol. 9 (9), pp. 2034-47. Date of Electronic Publication: 2009 Jul 22. |
| DOI: |
10.1111/j.1600-6143.2009.02757.x |
| Abstrakt: |
Inflammation and cancer are associated with impairment of T-cell responses by a heterogeneous population of myeloid-derived suppressor cells (MDSCs) coexpressing CD11b and GR-1 antigens. MDSCs have been recently implicated in costimulation blockade-induced transplantation tolerance in rats, which was under the control of inducible NO synthase (iNOS). Herein, we describe CD11b+GR-1+MDSC-compatible cells appearing after repetitive injections of lipopolysaccharide (LPS) using a unique mechanism of suppression. These cells suppressed T-cell proliferation and Th1 and Th2 cytokine production in both mixed lymphocyte reaction and polyclonal stimulation assays. Transfer of CD11b+ cells from LPS-treated mice in untreated recipients significantly prolonged skin allograft survival. They produced large amounts of IL-10 and expressed heme oxygenase-1 (HO-1), a stress-responsive enzyme endowed with immunoregulatory and cytoprotective properties not previously associated with MDSC activity. HO-1 inhibition by the specific inhibitor, SnPP, completely abolished T-cell suppression and IL-10 production. In contrast, neither iNOS nor arginase 1 inhibition did affect suppression. Importantly, HO-1 inhibition before CD11b+ cell transfer prevented the delay of allograft rejection revealing a new MDSC-associated suppressor mechanism relevant for transplantation. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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