Tumor-induced myeloid-derived suppressor cell subsets exert either inhibitory or stimulatory effects on distinct CD8+ T-cell activation events.

Tumor growth coincides with an accumulation of myeloid-derived suppressor cells (MDSCs) which exert immune suppression and which consist of two main subpopulations, known as monocytic CD11b+ CD115+ Ly6G- Ly6Chigh MO-MDSCs and granulocytic CD11b+ CD115- Ly6G+ Ly6Cint PMN-MDSCs. However, whether these distinct MDSC subsets hamper all aspects of early CD8+ T-cell activation - including cytokine production, surface marker expression, survival and cytotoxicity - is currently unclear. Here, employing an in vitro co-culture system, we demonstrate that splenic MDSC subsets suppress antigen-driven CD8+ T-cell proliferation, but differ in their dependency on IFN-gamma, STAT-1, IRF-1 and NO to do so. Moreover, MO- and PMN-MDSCs diminish IL-2 levels, but only MO-MDSCs affect IL-2R? (CD25) expression and STAT-5 signaling. Unexpectedly however, both MDSC populations stimulate IFN-gamma production by CD8+ T cells on a per-cell basis, illustrating that some T-cell activation characteristics are actually stimulated by MDSCs. Conversely, MO-MDSCs counteract the activation-induced change in CD44, CD62L, CD162 and granzyme B expression, while promoting CD69 and Fas upregulation. Together, these effects result in an altered CD8+ T-cell adhesiveness to the extracellular matrix and selectins, sensitivity to FasL-mediated apoptosis and cytotoxicity. Hence, MDSCs intricately influence different CD8+ T-cell activation events in vitro, whereby some parameters are suppressed while others are stimulated. This article is protected by copyright. All rights reserved.

Publication year:2013

Keywords:CD8+ T-cell activation, CD8+ T-cell suppression, monocytic myeloid-derived suppressor cell (MO-MDSC, nitric oxide, polymorphonuclear MDSC (PMN-MDSC), Immunology