Lymph node-resident lymphatic endothelial cells mediate peripheral tolerance via Aire-independent direct antigen presentation. 2010

Jarish N Cohen, and Cynthia J Guidi, and Eric F Tewalt, and Hui Qiao, and Sherin J Rouhani, and Alanna Ruddell, and Andrew G Farr, and Kenneth S Tung, and Victor H Engelhard
Department of Microbiology and Carter Immunology Center, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.

Peripheral immune tolerance is generally thought to result from cross-presentation of tissue-derived proteins by quiescent tissue-resident dendritic cells to self-reactive T cells that have escaped thymic negative selection, leading to anergy or deletion. Recently, we and others have implicated the lymph node (LN) stroma in mediating CD8 T cell peripheral tolerance. We demonstrate that LN-resident lymphatic endothelial cells express multiple peripheral tissue antigens (PTAs) independent of the autoimmune regulator (Aire). They directly present an epitope derived from one of these, the melanocyte-specific protein tyrosinase, to tyrosinase-specific CD8 T cells, leading to their deletion. We also show that other LN stromal subpopulations express distinct PTAs by mechanisms that vary in their Aire dependence. These results establish lymphatic endothelial cells, and potentially other LN-resident cells, as systemic mediators of peripheral immune tolerance.

UI MeSH Term Description Entries
D007108 Immune Tolerance The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc. Immunosuppression (Physiology),Immunosuppressions (Physiology),Tolerance, Immune
D008198 Lymph Nodes They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system. Lymph Node,Node, Lymph,Nodes, Lymph
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D008562 Membrane Glycoproteins Glycoproteins found on the membrane or surface of cells. Cell Surface Glycoproteins,Surface Glycoproteins,Cell Surface Glycoprotein,Membrane Glycoprotein,Surface Glycoprotein,Glycoprotein, Cell Surface,Glycoprotein, Membrane,Glycoprotein, Surface,Glycoproteins, Cell Surface,Glycoproteins, Membrane,Glycoproteins, Surface,Surface Glycoprotein, Cell,Surface Glycoproteins, Cell
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D009363 Neoplasm Proteins Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm. Proteins, Neoplasm
D011948 Receptors, Antigen, T-Cell Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (CD3 COMPLEX). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains. Antigen Receptors, T-Cell,T-Cell Receptors,Receptors, T-Cell Antigen,T-Cell Antigen Receptor,T-Cell Receptor,Antigen Receptor, T-Cell,Antigen Receptors, T Cell,Receptor, T-Cell,Receptor, T-Cell Antigen,Receptors, T Cell Antigen,Receptors, T-Cell,T Cell Antigen Receptor,T Cell Receptor,T Cell Receptors,T-Cell Antigen Receptors
D005968 Glutamate Decarboxylase A pyridoxal-phosphate protein that catalyzes the alpha-decarboxylation of L-glutamic acid to form gamma-aminobutyric acid and carbon dioxide. The enzyme is found in bacteria and in invertebrate and vertebrate nervous systems. It is the rate-limiting enzyme in determining GAMMA-AMINOBUTYRIC ACID levels in normal nervous tissues. The brain enzyme also acts on L-cysteate, L-cysteine sulfinate, and L-aspartate. EC 4.1.1.15. Glutamate Carboxy-Lyase,Glutamic Acid Decarboxylase,Acid Decarboxylase, Glutamic,Carboxy-Lyase, Glutamate,Decarboxylase, Glutamate,Decarboxylase, Glutamic Acid,Glutamate Carboxy Lyase
D000096927 AIRE Protein A transcriptional regulator primarily expressed in medullary thymic epithelial cells. It plays an important role in immunity by regulating the expression of a wide array of SELF-ANTIGENS and negative selection of autoreactive T-cells in the thymus. Deficiency in this protein induces a rare autosomal-recessive disease called AUTOIMMUNE POLYENDOCRINOPATHY-CANDIDIASIS-ECTODERMAL DYSTROPHY. APECED Protein,Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy Protein,Autoimmune Regulator Protein,Protein, AIRE,Protein, APECED,Protein, Autoimmune Regulator,Regulator Protein, Autoimmune

Related Publications

Jarish N Cohen, and Cynthia J Guidi, and Eric F Tewalt, and Hui Qiao, and Sherin J Rouhani, and Alanna Ruddell, and Andrew G Farr, and Kenneth S Tung, and Victor H Engelhard
September 2020, Nature reviews. Immunology,
Jarish N Cohen, and Cynthia J Guidi, and Eric F Tewalt, and Hui Qiao, and Sherin J Rouhani, and Alanna Ruddell, and Andrew G Farr, and Kenneth S Tung, and Victor H Engelhard
July 2017, Immunity,
Jarish N Cohen, and Cynthia J Guidi, and Eric F Tewalt, and Hui Qiao, and Sherin J Rouhani, and Alanna Ruddell, and Andrew G Farr, and Kenneth S Tung, and Victor H Engelhard
January 2011, The Journal of experimental medicine,
Jarish N Cohen, and Cynthia J Guidi, and Eric F Tewalt, and Hui Qiao, and Sherin J Rouhani, and Alanna Ruddell, and Andrew G Farr, and Kenneth S Tung, and Victor H Engelhard
December 2004, Trends in immunology,
Jarish N Cohen, and Cynthia J Guidi, and Eric F Tewalt, and Hui Qiao, and Sherin J Rouhani, and Alanna Ruddell, and Andrew G Farr, and Kenneth S Tung, and Victor H Engelhard
November 2014, eLife,
Jarish N Cohen, and Cynthia J Guidi, and Eric F Tewalt, and Hui Qiao, and Sherin J Rouhani, and Alanna Ruddell, and Andrew G Farr, and Kenneth S Tung, and Victor H Engelhard
January 2019, Frontiers in immunology,
Jarish N Cohen, and Cynthia J Guidi, and Eric F Tewalt, and Hui Qiao, and Sherin J Rouhani, and Alanna Ruddell, and Andrew G Farr, and Kenneth S Tung, and Victor H Engelhard
February 2002, Seminars in cell & developmental biology,
Jarish N Cohen, and Cynthia J Guidi, and Eric F Tewalt, and Hui Qiao, and Sherin J Rouhani, and Alanna Ruddell, and Andrew G Farr, and Kenneth S Tung, and Victor H Engelhard
January 2023, Trends in immunology,
Jarish N Cohen, and Cynthia J Guidi, and Eric F Tewalt, and Hui Qiao, and Sherin J Rouhani, and Alanna Ruddell, and Andrew G Farr, and Kenneth S Tung, and Victor H Engelhard
September 1999, The Journal of investigative dermatology,
Jarish N Cohen, and Cynthia J Guidi, and Eric F Tewalt, and Hui Qiao, and Sherin J Rouhani, and Alanna Ruddell, and Andrew G Farr, and Kenneth S Tung, and Victor H Engelhard
January 2009, Advances in experimental medicine and biology,
Copied contents to your clipboard!