| First Author | Schouppe E | Year | 2013 |
| Journal | Eur J Immunol | Volume | 43 |
| Issue | 11 | Pages | 2930-42 |
| PubMed ID | 23878002 | Mgi Jnum | J:203011 |
| Mgi Id | MGI:5523758 | Doi | 10.1002/eji.201343349 |
| Citation | Schouppe E, et al. (2013) Tumor-induced myeloid-derived suppressor cell subsets exert either inhibitory or stimulatory effects on distinct CD8(+) T-cell activation events. Eur J Immunol 43(11):2930-42 |
| abstractText | 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 (MO) CD11b(+) CD115(+) Ly6G(-) Ly6C(high) MDSCs and granulocytic CD11b(+) CD115(-) Ly6G(+) Ly6C(int) polymorphonuclear (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 coculture 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-MDSC and PMN-MDSCs diminish IL-2 levels, but only MO-MDSCs affect IL-2Ralpha (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. |
