Fletcher, AL, Lukacs-Kornek, V, Reynoso, ED, Pinner, SE, Bellemare-Pelletier, A, Curry, MS et al.. Lymph node fibroblastic reticular cells directly present peripheral tissue antigen under steady-state and inflammatory conditions. J Exp Med 207: 689-697

Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Journal of Experimental Medicine (Impact Factor: 12.52). 03/2010; 207(4):689-97. DOI: 10.1084/jem.20092642
Source: PubMed


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.

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    • "Tregs, in turn, prevented immune activation, which was required for graft acceptance. Importantly, in contrast with previous reports (Lee et al., 2007; Nichols et al., 2007; Magnusson et al., 2008; Cohen et al., 2010; Fletcher et al., 2010), in vivo immune regulation by self-antigen-expressing lymph node stromal cells in our transplantation setting was not related to self-reactive T cell deletion, suggesting that lymph node stromal cells may use multiple mechanisms to control self-reactivity. "
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    eLife Sciences 11/2014; 3. DOI:10.7554/eLife.04433 · 9.32 Impact Factor
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    • "In contrast to the chronic cellular compound, TLOs can be defined by the following criteria: TLOs (also known as ectopic lymphoid structures) represent highly organized lymphoid cell formations similar to secondary lymphoid organs like lymph nodes or the spleen. The structures of TLOs form a specific, well-organized network including fibroblast reticular cells in the T cell area that warrant optimal interactions of immune cells like antigen presentation, stimulation, and cell differentiation (Fletcher et al., 2010). Similar to lymph nodes, TLOs contain a mesenchymal network promoting lymphocyte homing. "
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    Frontiers in Physiology 08/2014; 5:296. DOI:10.3389/fphys.2014.00296 · 3.53 Impact Factor
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    • "It is now well established that particular stromal cells called lymphoid tissue organizer cells (LTo) collaborate with lymphoid tissue inducer cells (LTi) of hematopoietic origin for the development of secondary lymphoid organs (SLOs) during embryogenesis, and for the formation of TLOs in the context of chronic inflammatory diseases [10]–[12]. These stromal LTo were described as expressing various molecules such as gp38 (podoplanin), MadCAM1, ICAM1 or VCAM1 [13], [14], and following their activation, promote the recruitment of lymphocytes thus organizing the future lymphoid structure. The nature of LTi cells in the context of TLO genesis remains more of a debate and could differ depending on the tissue and the pathological setting [10]. "
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