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.
Original language | English |
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Pages (from-to) | 689-97 |
Number of pages | 9 |
Journal | The Journal of Experimental Medicine |
Volume | 207 |
Issue number | 4 |
DOIs | |
Publication status | Published - 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