Immune Tolerance Present and Clear Danger

ReseaRch highlights

ImmuNE tOLERANCE Present and clear danger

Several studies have suggested a Next, the authors examined mice, but remained constant in mice role for plasmacytoid dendritic cells whether pDCs affected T cell with MHC class II-deficient pDCs. (pDCs) in tolerogenic immune priming in the draining lymph nodes. Additional experiments suggested responses, but whether this is due During EAE, increased frequencies that pDCs promoted tolerogenic to innate functions of pDCs or is a of MOG-specific interferon-γ- and responses by expanding pre-existing

result of their antigen-presenting interleukin-17-producing T cells were natural TReg cell populations, rather role has remained unclear. Irla et al. detected in lymph node cultures from than by inducing de novo FOXP3 now show that pDCs can expand mice with MHC class II-deficient expression.

regulatory T (TReg) cells in an antigen- pDCs. Histological analyses indicated Finally, the authors showed that specific manner and ameliorate that pDCs were recruited to the T cell the transfer of CD4+CD25+ T cells inflammation during myelin oligo- zone of draining lymph nodes and from mice with EAE could decrease dendrocyte glycoprotein (MOG)- could interact in an antigen-specific EAE induction in recipient animals, induced experimental autoimmune manner with CD4+ T cells. Lack of but no protective effect was seen if encephalomyelitis (EAE). MHC class II expression did not CD4+CD25+ T cells were transferred Initial experiments indicated that prevent pDCs from localizing to the from diseased mice with MHC EAE development was exacerbated T cell zones of draining lymph nodes class II-deficient pDCs. Taken in mice when pDCs and B cells during EAE, but resulted in pDCs together, these data show that pDCs were unable to express MHC class II establishing fewer antigen-specific can act as antigen-presenting cells molecules, and additional work sug- contacts with CD4+ T cells. during adaptive immune responses gested that MHC class II-expressing One possible explanation for and promote tolerance by expanding

pDCs, rather than B cells, were these findings was that pDCs were TReg cell populations.

most important for alleviating promoting TReg cell functions in an Yvonne Bordon inflammation. In further support antigen-specific manner. Indeed, ORIGINAL RESEARCH PAPER Irla, M. et al. of this, transfer of MOG peptide- during EAE induction the frequency MHC class II-restricted antigen presentation by loaded pDCs, but not MHC class II- of proliferating forkhead box P3 plasmacytoid dendritic cells inhibits T cell- deficient pDCs, ameliorated EAE (FOXP3)+ T cells increased in the mediated autoimmunity. J. Exp. Med. 9 Aug 2010 Reg (doi:10.1084/jem.20092627) disease in wild-type recipients. draining lymph nodes of wild-type