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Ectopic lymphoid follicles

Kristina J H Kleinwort, Barbara Amann, Stefanie M Hauck, Regina Feederle, Walter Sekundo, Cornelia A Deeg
PURPOSE: Recently, formation of tertiary lymphoid structures was demonstrated and further characterized in the R161H mouse model of spontaneous autoimmune uveitis. In the horse model of spontaneous recurrent uveitis, intraocular lymphoid follicle formation is highly characteristic, and found in all stages and scores of disease, but in depth analyses of immunologic features of these structures are lacking to date. METHODS: Paraffin-embedded eye sections of cases with equine spontaneous recurrent uveitis (ERU) were characterized with immunohistochemistry to gain insight into the distribution, localization, and signaling of immune cells in intraocular tertiary lymphoid tissues...
August 1, 2016: Investigative Ophthalmology & Visual Science
Barbara Serafini, Barbara Rosicarelli, Caterina Veroni, Ling Zhou, Camilla Reali, Francesca Aloisi
Ectopic B-cell follicle-like structures (ELS) are found in the meninges of patients with secondary progressive multiple sclerosis (SPMS). Because cells expressing the transcriptional regulator retinoic acid receptor-related orphan receptor-γt (RORγt) and producing interleukin 17 (IL17), e.g. T helper 17 cells and lymphoid tissue inducer (LTi) cells, have been implicated in the formation of ELS, we studied RORγt and IL17 expression in brain tissue from patients with SPMS an assessed their relationships to immune infiltrates and meningeal ELS...
September 2016: Journal of Neuropathology and Experimental Neurology
Marc Clement, Adrien Galy, Patrick Bruneval, Marion Morvan, Fabien Hyafil, Khadija Benali, Nicoletta Pasi, Lydia Deschamps, Quentin Pellenc, Thomas Papo, Antonino Nicoletti, Karim Sacre
OBJECTIVE: The role of B cells in the pathogenesis of Takayasu arteritis (TA) is controversial. We aimed to study the presence of tertiary lymphoid organs (TLOs) in the aortic wall of TA patients. METHODS: Hematoxylin and eosin-stained sections from aorta specimens from patients with TA were screened for TLOs. The presence of B cell aggregates (CD20), follicular dendritic cells (FDCs, CD21), and high endothelial venules (HEVs, PNAd) was investigated by immunohistochemistry...
2016: Frontiers in Immunology
Ming Zeng, Anthony J Smith, Liang Shang, Stephen W Wietgrefe, James E Voss, John V Carlis, Qingsheng Li, Michael Piatak, Jeffrey D Lifson, R Paul Johnson, Ashley T Haase
Live attenuated vaccines such as SIV with a deleted nef gene have provided the most robust protection against subsequent vaginal challenge with wild-type (WT) SIV in the SIV-rhesus macaque model of HIV-1 transmission to women. Hence, identifying correlates of this protection could enable design of an effective HIV-1 vaccine. One such prechallenge correlate of protection from vaginal challenge has recently been identified as a system with three components: 1) IgG Abs reacting with the viral envelope glycoprotein trimeric gp41; 2) produced by plasma cells in the submucosa and ectopic tertiary lymphoid follicles in the ectocervix and vagina; and 3) concentrated on the path of virus entry by the neonatal FcR in the overlying epithelium...
March 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Carlos Alfaro, Jose I Echeveste, Maria E Rodriguez-Ruiz, Jose L Solorzano, Jose L Perez-Gracia, Miguel A Idoate, Jose M Lopez-Picazo, Alfonso R Sanchez-Paulete, Sara Labiano, Ana Rouzaut, Carmen Oñate, Angela Aznar, Maria D Lozano, Ignacio Melero
CD137 (4-1BB) is a surface protein initially discovered to mark activated T lymphocytes. However, its broader expression pattern also encompasses activated NK cells, B cells and myeloid cells, including mature dendritic cells. In this study, we have immunostained for CD137 on paraffin-embedded lymphoid tissues including tonsils, lymph nodes, ectopic tertiary lymphoid tissue in Hashimoto thyroiditis and cancer. Surprisingly, immunostaining mainly decorated intrafollicular lymphocytes in the tissues analyzed, with only scattered staining in interfollicular areas...
December 2015: Oncoimmunology
Gareth W Jones, Simon A Jones
Lymphoid neogenesis is traditionally viewed as a pre-programmed process that promotes the formation of lymphoid organs during development. Here, the spatial organization of T and B cells in lymph nodes and spleen into discrete structures regulates antigen-specific responses and adaptive immunity following immune challenge. However, lymphoid neogenesis is also triggered by chronic or persistent inflammation. Here, ectopic (or tertiary) lymphoid organs frequently develop in inflamed tissues as a response to infection, auto-immunity, transplantation, cancer or environmental irritants...
February 2016: Immunology
Lu Wang, Wei-Ping Zhang, Li Yao, Wei Zhang, Jin Zhu, Wei-Chen Zhang, Yue-Hua Zhang, Zhe Wang, Qing-Guo Yan, Ying Guo, Lin-Ni Fan, Yi-Xiong Liu, Gao-Sheng Huang
Ectopic lymphoid follicle infiltration is a key event in Hashimoto thyroiditis (HT). Positive regulatory domain zinc finger protein 1 (PRDM1), which is induced by antigen stimulation, can regulate all lymphocyte lineages. Several groups independently demonstrated that human parvovirus B19 (PVB19) is closely associated with HT. Hence, we determined whether PRDM1 is expressed in HT thyroid tissue and whether there is any correlation between PRDM1 expression and PVB19 in the pathogenesis of HT. We detected PRDM1 expression in HT (n = 86), normal thyroid tissue (n = 30), and nontoxic nodular goiter (n = 20) samples using immunohistochemistry...
December 2015: Human Pathology
Julianne K Hatfield, Melissa A Brown
Innate lymphoid cells are immune cells that reside in tissues that interface with the external environment and contribute to the first line defense against pathogens. However, they also have roles in promoting chronic inflammation. Here we demonstrate that group 3 ILCs, (ILC3s - CD45+Lin-IL-7Rα+RORγt+), are normal residents of the meninges and exhibit disease-induced accumulation and activation in EAE. In addition to production of the pro-inflammatory cytokines IL-17 and GM-CSF, ILC3s constitutively express CD30L and OX40L, molecules required for memory T cell survival...
October 2015: Cellular Immunology
Juan D Cañete, Raquel Celis, Nataliya Yeremenko, Raimon Sanmartí, Leonie van Duivenvoorde, Julio Ramírez, Iris Blijdorp, Carmen M García-Herrero, José L Pablos, Dominique L Baeten
INTRODUCTION: The functional relevance of synovial ectopic lymphoid neogenesis (ELN) in rheumatoid arthritis (RA) remains unknown. As ELN correlates with the degree of tissue inflammation, we investigated whether ELN was associated with specific cytokine profiles. METHODS: Synovial ELN was determined by immunohistology and long CD21 isoform (CD21L) expression. Cytokine expression was determined by multiplex enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (PCR) as well as immunohistology in synovial fluid (SF) (n = 44) and tissue (ST) (n = 108), respectively...
2015: Arthritis Research & Therapy
Ekaterina Klimatcheva, Tracy Pandina, Christine Reilly, Sebold Torno, Holm Bussler, Maria Scrivens, Alan Jonason, Crystal Mallow, Michael Doherty, Mark Paris, Ernest S Smith, Maurice Zauderer
BACKGROUND: Homeostatic B Cell-Attracting chemokine 1 (BCA-1) otherwise known as CXCL13 is constitutively expressed in secondary lymphoid organs by follicular dendritic cells (FDC) and macrophages. It is the only known ligand for the CXCR5 receptor, which is expressed on mature B cells, follicular helper T cells (Tfh), Th17 cells and regulatory T (Treg) cells. Aberrant expression of CXCL13 within ectopic germinal centers has been linked to the development of autoimmune disorders (e.g...
2015: BMC Immunology
Josefine Radke, Debora Pehl, Eleonora Aronica, Dieneke Schonenberg-Meinema, Udo Schneider, Frank L Heppner, Marianne de Visser, Hans H Goebel, Werner Stenzel
OBJECTIVE: To investigate the clinical and morphologic spectrum of early adult-onset dermatomyositis (DM), an inflammatory disease that affects small vessels of the muscle and the skin. METHODS: Histologic evaluation of frozen muscle samples was employed to visualize the cellular organization of ectopic lymphoid structures in muscle biopsies obtained from 2 patients diagnosed with DM. Clinical presentation and morphologic features, as well as treatment and follow-up, were assessed and documented...
August 2014: Neurology® Neuroimmunology & Neuroinflammation
Qingsheng Li, Ming Zeng, Lijie Duan, James E Voss, Anthony J Smith, Stefan Pambuccian, Liang Shang, Stephen Wietgrefe, Peter J Southern, Cavan S Reilly, Pamela J Skinner, Mary L Zupancic, John V Carlis, Michael Piatak, Diane Waterman, R Keith Reeves, Katherine Masek-Hammerman, Cynthia A Derdeyn, Michael D Alpert, David T Evans, Heinz Kohler, Sybille Müller, James Robinson, Jeffrey D Lifson, Dennis R Burton, R Paul Johnson, Ashley T Haase
We sought design principles for a vaccine to prevent HIV transmission to women by identifying correlates of protection conferred by a highly effective live attenuated SIV vaccine in the rhesus macaque animal model. We show that SIVmac239Δnef vaccination recruits plasma cells and induces ectopic lymphoid follicle formation beneath the mucosal epithelium in the rhesus macaque female reproductive tract. The plasma cells and ectopic follicles produce IgG Abs reactive with viral envelope glycoprotein gp41 trimers, and these Abs are concentrated on the path of virus entry by the neonatal FcR in cervical reserve epithelium and in vaginal epithelium...
September 15, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
Jodi L Karnell, Tamer I Mahmoud, Ronald Herbst, Rachel Ettinger
Ectopic follicles are non-encapsulated organized lymphoid structures that form at sites of inflammation and presumably contribute to the activation and differentiation of cells with autoreactive potential within target tissues. As such, directed targeting of ectopic follicles in settings of autoimmunity may provide a means to specifically inhibit the activation of autoreactive cells without impairing protective immune responses ongoing in peripheral lymphoid tissues. NOD·H2h4 mice are a non-diabetic strain of NOD mice which develop a Sjögren's syndrome-like disease which includes the formation of ectopic follicles in the salivary gland and characteristic Sjögren's autoantibodies...
December 2014: Molecular Immunology
Anastasia Meshcheryakova, Dietmar Tamandl, Erika Bajna, Judith Stift, Martina Mittlboeck, Martin Svoboda, Denise Heiden, Stefan Stremitzer, Erika Jensen-Jarolim, Thomas Grünberger, Michael Bergmann, Diana Mechtcheriakova
Remarkably limited information is available about biological mechanisms that determine the disease entity of metastatic colorectal cancer in the liver (CRCLM) with no good clinical parameters to estimate prognosis. For the last few years, understanding the relationship between tumor characteristics and local immune response has gained increasing attention. Given the multifaceted roles of B-cell-driven responses, we aimed to elucidate the immunological imprint of B lymphocytes at the metastatic site, the interrelation with macrophages, and their prognostic relevance...
2014: PloS One
Andrea Ladányi, Tímea Sebestyén, Anita Mohos, Gabriella Liszkay, Beáta Somlai, Erika Tóth, József Tímár
Ectopic lymphoid structures have been described in several tumor types including metastatic lesions, but not primary tumors, of patients with melanoma. Here we present evidence of B-cell follicles in primary cutaneous melanomas, being present in 39 of 147 cases (27 %). B-cell clusters were associated with T lymphocytes, most of which belonging to CD45RO(+) memory T cells. A network of CD21(+) follicular dendritic cells was demonstrated in 8 of 22 cases studied (36 %). MECA-79(+) HEV-like venules were observed in the neighborhood of the follicles in the majority of cases, however, their presence was not confined to tumors hosting ectopic lymphoid structures...
October 2014: Pathology Oncology Research: POR
Henrike Fleige, Sarina Ravens, Georgios Leandros Moschovakis, Jasmin Bölter, Stefanie Willenzon, Gerd Sutter, Susanne Häussler, Ulrich Kalinke, Immo Prinz, Reinhold Förster
Ectopic lymphoid tissue, such as bronchus-associated lymphoid tissue (BALT) in the lung, develops spontaneously at sites of chronic inflammation or during infection. The molecular mechanisms underlying the neogenesis of such tertiary lymphoid tissue are still poorly understood. We show that the type of inflammation-inducing pathogen determines which key factors are required for the formation and maturation of BALT. Thus, a single intranasal administration of the poxvirus modified vaccinia virus Ankara (MVA) is sufficient to induce highly organized BALT with densely packed B cell follicles containing a network of CXCL13-expressing follicular DCs (FDCs), as well as CXCL12-producing follicular stromal cells...
April 7, 2014: Journal of Experimental Medicine
Felicia A Tucci, Ruth Broering, Melanie Lutterbeck, Joerg F Schlaak, Ralf Küppers
Chronic infection with hepatitis C virus (HCV) often affects the B-cell compartment, leading to the occurrence of autoimmunity and B-cell lymphoproliferation, in particular mixed cryoglobulinemia and B-cell lymphomas. HCV presumably causes these lymphoproliferations by chronic antigenic stimulation and/or direct mutagenic effects on B cells. It has been speculated that the interaction of HCV with B cells and the expansion of antigen-triggered B cells happens in germinal center-like structures in the livers of HCV carriers...
June 2014: European Journal of Immunology
Francesca Bergomas, Fabio Grizzi, Andrea Doni, Samantha Pesce, Luigi Laghi, Paola Allavena, Alberto Mantovani, Federica Marchesi
Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated...
2011: Cancers
Ganta Vijay Chaitanya, Seiichi Omura, Fumitaka Sato, Nicholas E Martinez, Alireza Minagar, Murali Ramanathan, Bianca Weinstock Guttman, Robert Zivadinov, Ikuo Tsunoda, Jonathan S Alexander
BACKGROUND: Multiple sclerosis (MS) is associated with ectopic lymphoid follicle formation. Podoplanin+ (lymphatic marker) T helper17 (Th17) cells and B cell aggregates have been implicated in the formation of tertiary lymphoid organs (TLOs) in MS and experimental autoimmune encephalitis (EAE). Since podoplanin expressed by Th17 cells in MS brains is also expressed by lymphatic endothelium, we investigated whether the pathophysiology of MS involves inductions of lymphatic proteins in the inflamed neurovasculature...
2013: Journal of Neuroinflammation
Davide Lucchesi, Michele Bombardieri
TLS, characterized by the formation of ectopic B/T cell follicles with FDCs supporting an ectopic GC response, have been described in the target organs of several autoimmune diseases, including MS, RA, SS, and autoimmune thyroiditis. These structures represent functional niches, whereby autoreactive B cells undergo in situ affinity maturation and differentiation to autoantibody-producing cells, thus contributing to the progression and persistence of autoimmunity. Increasing evidence demonstrates that TLS can also develop in the context of cancer, as well as chronic infections...
December 2013: Journal of Leukocyte Biology
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