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Reversal of the suppressive effect of BM-MDSCs on T-cell proliferation by inhibitors of inducible nitric oxide synthase (iNOS).

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posted on 2014-11-04, 22:19 authored by Júlia Kurkó, András Vida, Tímea Ocskó, Beata Tryniszewska, Tibor A. Rauch, Tibor T. Glant, Zoltán Szekanecz, Katalin Mikecz

Various inhibitors of MDSC effector molecules, including the arginase 1 inhibitor nor-NOHA, iNOS inhibitors L-NMMA and 1400W, the reactive oxygen species (ROS) scavenger catalase, and the caspase/apoptosis inhibitor Z-VAD-FMK, were used to inhibit the BM-MDSC-mediated suppression of (A) Ag (rhG1)-induced/DC-dependent and (B) anti-CD3/CD28-induced proliferation of PG-TCR-Tg T cells. The results (compiled from 2 independent series of experiments, each with 2 co-cultures) are expressed as percent suppression of T-cell proliferation in the presence (black bars) or absence (red bar) of inhibitors. While suppression of T-cell proliferation in both induction systems was significantly reversed by the iNOS inhibitors L-NMMA and 1400W (*p<0.0001 in all cases; Kruskal-Wallis test followed by Dunn’s multiple comparisons test), none of the other inhibitors had a significant effect on BM-MDSC-mediated suppression of T cells.