Lymph node fibroblastic reticular cells directly present peripheral tissue antigen under steady-state and inflammatory conditions

Anne L Fletcher, Veronika Lukacs-Kornek, Erika D Reynoso, Sophie E Pinner, Angelique Bellemare-Pelletier, Mark S Curry, Ai-Ris Collier, Richard L Boyd, Shannon J Turley

Research output: Contribution to journalArticlepeer-review

231 Citations (Scopus)


Lymph node stromal cells (LNSCs) can induce potent, antigen-specific T cell tolerance under steady-state conditions. Although expression of various peripheral tissue-restricted antigens (PTAs) and presentation to naive CD8+ T cells has been demonstrated, the stromal subsets responsible have not been identified. We report that fibroblastic reticular cells (FRCs), which reside in the T cell zone of the LN, ectopically express and directly present a model PTA to naive T cells, inducing their proliferation. However, we found that no single LNSC subset was responsible for PTA expression; rather, each subset had its own characteristic antigen display. Studies to date have concentrated on PTA presentation under steady-state conditions; however, because LNs are frequently inflammatory sites, we assessed whether inflammation altered stromal cell-T cell interactions. Strikingly, FRCs showed reduced stimulation of T cells after Toll-like receptor 3 ligation. We also characterize an LNSC subset expressing the highest levels of autoimmune regulator, which responds potently to bystander inflammation by up-regulating PTA expression. Collectively, these data show that diverse stromal cell types have evolved to constitutively express PTAs, and that exposure to viral products alters the interaction between T cells and LNSCs.
Original languageEnglish
Pages (from-to)689-97
Number of pages9
JournalThe Journal of Experimental Medicine
Issue number4
Publication statusPublished - 12 Apr 2010


  • Animals
  • Antigen Presentation
  • Antigens, CD
  • Antigens, CD274
  • Antigens, CD80
  • Autoantigens
  • Cell Proliferation
  • Endothelial Cells
  • Gene Expression
  • Histocompatibility Antigens Class I
  • Immune Tolerance
  • Immunophenotyping
  • Inflammation
  • Lymph Nodes
  • Lymphocyte Activation
  • Male
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Ovalbumin
  • Peptides
  • Poly I-C
  • Stromal Cells
  • T-Lymphocytes
  • Toll-Like Receptor 3


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