| First Author | Antignano F | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 7 | Pages | e21893 |
| PubMed ID | 21755007 | Mgi Jnum | J:175809 |
| Mgi Id | MGI:5287343 | Doi | 10.1371/journal.pone.0021893 |
| Citation | Antignano F, et al. (2011) SHIP-deficient dendritic cells, unlike wild type dendritic cells, suppress T cell proliferation via a nitric oxide-independent mechanism. PLoS One 6(7):e21893 |
| abstractText | 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 SHIP-/- 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 SHIP-/- 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-/- murine DCs, derived under different conditions or isolated from spleens, with alphaCD3+ alphaCD28 activated WT T cells and determined the relative suppressive abilities of the different DC subsets. We found that, in contrast to SHIP+/+ and -/- splenic or Flt3L-derived DCs, which do not suppress T cell proliferation in vitro, both SHIP+/+ and -/- GM-DCs were capable of potently suppressing T cell proliferation. However, WT GM-DC suppression appeared to be mediated, at least in part, by nitric oxide (NO) production while SHIP-/- GM-DCs expressed high levels of arginase 1 and did not produce NO. Following exhaustive studies to ascertain the mechanism of SHIP-/- DC-mediated suppression, we could conclude that cell-cell contact was required and the mechanism may be related to their relative immaturity, compared to SHIP+/+ GM-DCs. CONCLUSIONS: These findings suggest that although both SHIP+/+ and -/- GM-DCs suppress T cell proliferation, the mechanism(s) employed are different. WT GM-DCs suppress, at least in part, via IFNgamma-induced NO production while SHIP-/- GM-DCs do not produce NO and suppression can only be alleviated when contact is prevented. |
