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

Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Journal of Experimental Medicine (Impact Factor: 13.21). 03/2010; 207(4):689-97. DOI: 10.1084/jem.20092642
Source: PubMed

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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The presence of adventitial inflammation in correlation with atherosclerotic lesions has been recognized for decades. In the last years, several studies have investigated the relevance and impact of adventitial inflammation on atherogenesis. In the abdominal aorta of elderly Apoe(-/-) mice, adventitial inflammatory structures were characterized as organized ectopic lymphoid tissue, and therefore termed adventitial tertiary lymphoid organs (ATLOs). These ATLOs possess similarities in development, structure and function to secondary lymphoid organs. A crosstalk between intimal atherosclerotic lesions and ATLOs has been suggested, and several studies could demonstrate a potential role for medial vascular smooth muscle cells in this process. We here review the development, phenotypic characteristics, and function of ATLOs in atherosclerosis. Furthermore, we discuss the possible role of medial vascular smooth muscle cells and their interaction between plaque and ATLOs.
    Frontiers in physiology. 01/2014; 5:296.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Lymphatic vessels are routes for leukocyte migration and fluid drainage. In addition to their passive roles in migration of leukocytes, increasing evidence indicates their active roles in immune regulation. Tissue inflammation rapidly induces lymphatic endothelial cell proliferation and chemokine production, thereby resulting in lymphangiogenesis. Furthermore, lymphatic endothelial cells induce T cell tolerance through various mechanisms. In this review, we focus on the current knowledge on how inflammatory cytokines affect lymphangiogenesis and the roles of lymphatic vessels in modulating immune responses.
    Immune Network 08/2014; 14(4):182-6.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Lymph node (LN) is the sites where mature lymphocytes become stimulated to respond to invading pathogens in the body. Lymphocytes screen the surfaces of pathogen-carrying antigen-presenting cells for cognate antigens, while moving along stromal structural back bone. Fibroblastic reticular cells (FRC) is stromal cell forming the 3 dimensional structure networks of the T cell rich zones in LN, and provide a guidance path for immigrating T lymphocytes. In these cooperative environments, the cell to cell bidirectional interactions between FRC and T cells in LN are therefore essential to the normal functioning of these tissues. Not only do FRCs physically construct LN architecture but they are essential for regulating T cell biology within these domains. FRC interact closely with T lymphocytes, is providing scaffolds, secreting soluble factors including cytokine in which FRCs influence T cell immune response. More recently, FRC have been found to induce peripheral T cell tolerance and regulate the extent to which newly activated T cells proliferate within LN. Thus, FRC-T cell crosstalk has important consequences for regulating immune cell function within LN. In addition, FRC have profound effects on innate immune response by secreting anti-microbial peptides and complement, etc in the inflammatory milieu. In summary, we propose a model in which FRC engage in a bidirectional touch to increase the T cell biological efficiency between FRC and T cells. This collaborative feedback loop may help to maintain tissue function during inflammation response.
    Journal of Life Science. 01/2013; 23(11).

Full-text (3 Sources)

Available from
May 23, 2014