ship-deficient dendritic cells, unlike wild type dendritic cells, suppress t cell proliferation via a nitric oxide-independent mechanismship-deficient树突细胞,与野生型树突细胞,通过oxide-independent氮抑制t细胞增殖的机制.pdfVIP

SHIP-Deficient Dendritic Cells, Unlike Wild Type Dendritic Cells, Suppress T Cell Proliferation via a Nitric Oxide-Independent Mechanism 1,2 1 3 1 1 3 Frann Antignano , Melisa Hamilton , Scott Patterson , Victor Ho , Carla Cohen , Megan K. Levings , Gerald Krystal1* 1The Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada, 2 The Biomedical Research Centre, The University of British Columbia, Vancouver, British Columbia, Canada, 3 Department of Surgery, The University of British Columbia and Immunity in Health and Disease, Child and Family Research Institute, B.C. Children’s Hospital, Vancouver, British Columbia, Canada Abstract Background: Dendritic cells (DCs) not only play a crucial role in activating immune cells but also suppressing them. We recently investigated SHIP’s role in murine DCs in terms of immune cell activation and found that TLR agonist-stimulated SHIP2/ 2 GM-CSF-derived DCs (GM-DCs) were far less capable than wild type (WT, SHIP+/+) GM-DCs at activating T cell proliferation. This was most likely because SHIP2/ 2 GM-DCs could not up-regulate MHCII and/or co-stimulatory receptors following TLR stimulation. However, the role of SHIP in DC-induced T cell suppression was not investigated. Methodology/Principal Findings: In this study we examined SHIP’s role in DC-induced T cell suppression by co-culturing WT and SHIP 2/ 2 murine DCs, derived under different conditions or isolated from spleens, with aCD3+ aCD28 activated WT T cells and determined the relative suppressive abilities of the different DC subsets. We found that, in contrast to SHIP+/+ and 2/ 2 splenic or Flt3L-derived DCs, which do not suppress T cell proliferation in vitro, both SHIP+/+ and 2/