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. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.