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

Research output: Contribution to journalArticlepeer-review

Authors

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

Colleges, School and Institutes

Abstract

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.

Details

Original languageEnglish
Pages (from-to)689-97
Number of pages9
JournalThe Journal of Experimental Medicine
Volume207
Issue number4
Publication statusPublished - 12 Apr 2010

Keywords

  • 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