title: In vivo suppressive function of myeloid-derived suppressor cells is limited to the inflammatory site.
abstract: Current paradigms suggest that, despite the heterogeneity of myeloid-derived suppressor cells (MDSC), all Gr-1(+) CD11b(+) cells can exert suppressive function when exposed to inflammatory stimuli. In vitro evaluation shows that MDSC from multiple tissue sites have suppressive activity, and in vivo inhibition of MDSC enhances T-cell function; however, the relative capacity of MDSC present at localized inflammatory sites or in peripheral tissues to suppress T-cell responses in vivo has not been directly evaluated. In the current study, we observed that during a tissue-specific inflammatory response, MDSC inhibition of CD8(+) T-cell proliferation and IFN-γ production was restricted to the inflammatory site. Using a prostate-specific inflammatory model and a heterotopic prostate tumor model, we showed that MDSC from inflammatory sites or from tumor tissue possess immediate capacity to inhibit T-cell function, whereas those isolated from peripheral tissues (spleens and liver) were not suppressive without activation of iNOS by exposure to IFN-γ. These data suggest that MDSC are important regulators of immune responses in the prostate during acute inflammation and the chronic inflammatory setting of tumor growth, and that regulation of T-cell function by MDSC during a localized inflammatory response is restricted in vivo to the site of an ongoing immune response.
authors.affiliation: University of Iowa Immunology Program, Iowa City, IA, USA. haverkamp.j@gmail.com
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Haverkamp
authors.forename: Scott A
authors.initials: SA
authors.lastname: Crist
authors.forename: Bennett D
authors.initials: BD
authors.lastname: Elzey
authors.forename: Cansu
authors.initials: C
authors.lastname: Cimen
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Ratliff
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001119:Arginase / Q000235:genetics; D039481:CD11b Antigen / Q000378:metabolism; D049109:Cell Proliferation; D004195:Disease Models, Animal; D007108:Immune Tolerance; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000276:immunology* / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D011472:Prostatitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D039481:CD11b Antigen; C503133:Gr-1 protein, mouse; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D010047:Ovalbumin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C544448:Arg1 protein, mouse; D001119:Arginase