Modulation of CD8(+) T-cell activation events by monocytic and granulocytic myeloid-derived suppressor cells.
Myeloid-derived suppressor cells are immature myeloid cells, consisting of a monocytic and a granulocytic fraction, that are known to suppress anti-tumor immune responses. Important targets of the immunosuppressive capacity of MDSC are CD8(+) T cells, which are crucial cytotoxic effector cells in immunotherapeutic settings. CD8(+) T-cell activation and differentiation comprises a well-orchestrated series of events, starting from early TCR-mediated signaling and leading to cytokine secretion, the expression of activation markers, proliferation and the differentiation into several subsets of effector and memory cells. In this review, we summarize the available data on how the production of reactive oxygen species, nitric oxide, the arginase-mediated depletion of l-arginine and Cystine depletion by MDSCs interfere with the signaling molecules necessary for normal CTL differentiation and activation.
Laboratory of Myeloid Cell Immunology, VIB, Brussels, Belgium; Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
Elio
E
Schouppe
Eva
E
Van Overmeire
Damya
D
Laoui
Jiri
J
Keirsse
Jo A
JA
Van Ginderachter
D001119:Arginase / Q000378:metabolism; D001120:Arginine / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D003553:Cystine / Q000378:metabolism; D006098:Granulocytes / Q000276:immunology*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology
C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D017382:Reactive Oxygen Species; D011948:Receptors, Antigen, T-Cell; D009569:Nitric Oxide; D003553:Cystine; D001120:Arginine; D001119:Arginase
Arginase; Myeloid-derived suppressor cells; Nitric oxide; Reactive oxygen species; TCR signaling; iNOS; l-Arginine depletion