title: Myeloid-derived suppressor cells express the death receptor Fas and apoptose in response to T cell-expressed FasL.
abstract: Myeloid-derived suppressor cells (MDSCs) inhibit adaptive and innate immunity and accumulate in the blood of persons with cancer, chronic inflammation, trauma, infection, and stress. Some of the factors inducing their accumulation are known; however, mechanisms regulating their turnover have not been identified. Mass spectrometry showed prominent expression of apoptosis pathway proteins, suggesting that MDSC turnover may be regulated by Fas-FasL-mediated apoptosis. This hypothesis was confirmed by showing that blood MDSCs induced by 3 mouse tumors were Fas(+) and apoptosed in response to Fas agonist in vitro and to activated FasL(+) T cells in vivo. FasL-deficient mice contained significantly more blood MDSCs than FasL(+/+) mice, and after removal of primary tumors MDSCs regressed in STAT6(-/-) and CD1(-/-) mice but not in STAT6(-/-)FasL(-/-) or CD1(-/-)FasL(-/-) mice. Fas(+) macrophages and dendritic cells did not apoptose in response to activated T cells, indicating that Fas-FasL regulation of myeloid cells was restricted to MDSCs. These results identify a new mechanism regulating MDSC levels in vivo and show a retaliatory relationship between T cells and MDSCs in that MDSCs suppress T-cell activation; however, once activated, T cells mediate MDSC apoptosis.
authors: Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD, USA.
authors: Pratima
authors: P
authors: Sinha
authors: Olesya
authors: O
authors: Chornoguz
authors: Virginia K
authors: VK
authors: Clements
authors: Konstantin A
authors: KA
authors: Artemenko
authors: Roman A
authors: RA
authors: Zubarev
authors: Suzanne
authors: S
authors: Ostrand-Rosenberg
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D053222:Fas Ligand Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005260:Female; D008213:Lymphocyte Activation; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D053222:Fas Ligand Protein; C491899:Fas protein, mouse; C505658:Fasl protein, mouse; D019014:fas Receptor