Immune Tolerance New Peacekeepers Identified

ReseaRch highlights

ImmuNE tOLERANCE New peacekeepers identified

Lymph node stromal cells (LNSCs) To further understand the role antigen A33 and the pancreatic have been shown to be mediators of LNSC subsets in peripheral polypeptide PPY. Other PTAs were of antigen-specific peripheral T cell tolerance, the groups used different shown to be expressed by all four tolerance through the expression of systems to examine the induction subsets, highlighting the complexity peripheral tissue antigens (PTAs). of self tolerance to specific PTAs and specificity of PTA expression However, the specific cell subsets by each subset. The melanocyte- by LNSCs. involved were not known. Now, specific protein tyrosinase (TYR) Through the administration two papers published in the Journal was shown to be expressed by of the Toll-like receptor 3 ligand of Experimental Medicine have LECs but not by other LNSCs, polyinosinic–polycytidylic acid identified these cell subsets and and Cohen et al. showed that (polyI:C), Fletcher et al. showed some of the PTAs that they express, these cells induced proliferation of that PTA expression by FRCs was highlighting the importance of TYR-specific CD8+ T cells, which reduced and that stimulation of diverse LNSC subsets in maintaining is known to occur before T cell cognate T cells was decreased dur- peripheral tolerance. deletion in vivo. Using a model ing inflammation. They propose Peripheral tolerance is the process system in which LNSCs could that the decreased ability of FRCs by which self-reactive T cells that have express ovalbumin (OVA) as a PTA, to stimulate CD8+ T cells may be a escaped negative selection in the thy- Fletcher et al. showed that it was the mechanism to protect lymph node mus are rendered anergic or deleted in FRCs that predominantly presented structure and function during an the periphery. Analyses of the lymph this antigen to the corresponding inflammatory response. node stromal compartment by both CD8+ T cells, resulting in the T cell Together, these studies show that groups identified four phenotypi- proliferation that leads to deletion LNSCs of distinct origin, phenotype cally different cell subsets based on in this model. So, these data show and function can express distinct their expression of gp38 and CD31: that specific LNSC subsets can act endogenous antigens and potentially fibroblastic reticular cells (FRCs; as antigen-presenting cells for the act as mediators of peripheral gp38+CD31–), blood endothelial induction of peripheral tolerance. tolerance. cells (BECs; gp38–CD31+), lymphatic Furthermore, several other Olive Leavy endothelial cells (LECs; gp38+CD31+) PTAs were shown to be specifically and a poorly studied population of expressed by distinct LNSC subsets. ORIGINAL RESEARCH PAPERS Cohen, J. N. – – et al. Lymph node-resident lymphatic endothelial double negative cells (gp38 CD31 ). FRCs expressed the melanocyte- cells mediate peripheral tolerance via Aire- Of note, only the double negative cell specific antigen MLANA (also independent direct antigen presentation. J. Exp. subset expressed the transcription known as MART1) and prepro- Med. 22 Mar 2010 (doi:10.1084/jem.20092465) | Fletcher, A. L. et al. Lymph node fibroblastic factor autoimmune regulator (AIRE), insulin 2, whereas BECs specifically reticular cells directly present peripheral tissue which is known to be crucial for the expressed retinol S antigen. In antigen under steady-state and inflammatory expression of numerous PTAs by addition to TYR, LECs expressed conditions. J. Exp. Med. 22 Mar 2010 (doi:10.1084/ jem.20092642) thymic epithelial cells. the intestinal epithelial cell-specific